Trial Outcomes & Findings for Pharmacokinetics and Safety Study of BI 695502 in Healthy Subjects (NCT NCT01608087)

Last Updated: 2019-11-08

Results Overview

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented as adjusted geometric mean (gMean) and geometric coefficient of variation (%) (gCV%). Adjustment were made for treatment effect and weight.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

91 participants

Primary outcome timeframe

Pharmacokinetic samples were collected predose, just before the end of the infusion, 2, 4, and 8 hours after the start of the infusion

Results posted on

2019-11-08

Participant Flow

This was a randomized, single-blind, single-dose, parallel-arm, active comparator, Phase I clinical trial. The trial was planned to be conducted in two stages and subjects were to be randomly allocated in each stage. Based on the interim analysis finalized on 18 February 2013, the trial was closed after Stage 1, and Stage 2 was not conducted.

Subjects were randomized in a 1:1:1 ratio to receive BI 695502, United States (US)-licensed Avastin® or European Union (EU)-approved Avastin®.

Participant milestones

Participant milestones
Measure	BI 695502 (T) Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) BI 695502 concentrate for solution for infusion.	United States (US)-Licensed Avastin® (R1) Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) US-licensed Avastin® solution for intravenous infusion.	European Union (EU)-Approved Avastin® (R2) Subjects were administered a single dose of 25 microgram per millilitre (mg/mL) EU-approved Avastin® concentrate for solution for infusion.
Overall Study STARTED	30	30	31
Overall Study COMPLETED	30	28	31
Overall Study NOT COMPLETED	0	2	0

Reasons for withdrawal

Reasons for withdrawal
Measure	BI 695502 (T) Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) BI 695502 concentrate for solution for infusion.	United States (US)-Licensed Avastin® (R1) Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) US-licensed Avastin® solution for intravenous infusion.	European Union (EU)-Approved Avastin® (R2) Subjects were administered a single dose of 25 microgram per millilitre (mg/mL) EU-approved Avastin® concentrate for solution for infusion.
Overall Study Lost to Follow-up	0	1	0
Overall Study Other Reason	0	1	0

Baseline Characteristics

Pharmacokinetics and Safety Study of BI 695502 in Healthy Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	BI 695502 (T) n=30 Participants Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) BI 695502 concentrate for solution for infusion.	United States (US)-Licensed Avastin® (R1) n=30 Participants Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) US-licensed Avastin® solution for intravenous infusion.	European Union (EU)-Approved Avastin® (R2) n=31 Participants Subjects were administered a single dose of 25 microgram per millilitre (mg/mL) EU-approved Avastin® concentrate for solution for infusion.	Total n=91 Participants Total of all reporting groups
Age, Continuous	26.8 Years STANDARD_DEVIATION 6.5 • n=5 Participants	28.8 Years STANDARD_DEVIATION 8.1 • n=7 Participants	26.6 Years STANDARD_DEVIATION 5.4 • n=5 Participants	27.4 Years STANDARD_DEVIATION 6.7 • 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	30 Participants n=5 Participants	30 Participants n=7 Participants	31 Participants n=5 Participants	91 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants	15 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants	22 Participants n=7 Participants	22 Participants n=5 Participants	67 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Pharmacokinetic samples were collected predose, just before the end of the infusion, 2, 4, and 8 hours after the start of the infusion

Population: Pharmacokinetic (PK) set: The PK set included all subjects in the treated set (subjects who received at least one administration of trial medication) who provided at least one evaluable observation of a PK endpoint and had no important protocol violations relevant to the evaluation of PK biosimilarity.

Outcome measures

Outcome measures
Measure	BI 695502 (T) n=30 Participants Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) BI 695502 concentrate for solution for infusion.	United States (US)-Licensed Avastin® (R1) n=30 Participants Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) US-licensed Avastin® solution for intravenous infusion.	European Union (EU)-Approved Avastin® (R2) n=30 Participants Subjects were administered a single dose of 25 microgram per millilitre (mg/mL) EU-approved Avastin® concentrate for solution for infusion.
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞).	7013.010 microgram*hour/milliliter Geometric Coefficient of Variation 19.52	7261.119 microgram*hour/milliliter Geometric Coefficient of Variation 15.57	7649.491 microgram*hour/milliliter Geometric Coefficient of Variation 18.29

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected predose, just before the end of the infusion, 2, 4, and 8 hours after the start of the infusion

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point is presented as adjusted geometric mean (gMean) and geometric coefficient of variation (%) (gCV%). Adjustment was made for treatment effect and weight.

Outcome measures

Outcome measures
Measure	BI 695502 (T) n=30 Participants Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) BI 695502 concentrate for solution for infusion.	United States (US)-Licensed Avastin® (R1) n=30 Participants Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) US-licensed Avastin® solution for intravenous infusion.	European Union (EU)-Approved Avastin® (R2) n=30 Participants Subjects were administered a single dose of 25 microgram per millilitre (mg/mL) EU-approved Avastin® concentrate for solution for infusion.
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point (AUC0-tz)	6570.047 microgram*hour/milliliter Geometric Coefficient of Variation 20.68	6639.315 microgram*hour/milliliter Geometric Coefficient of Variation 18.46	7167.313 microgram*hour/milliliter Geometric Coefficient of Variation 19.72

SECONDARY outcome

Timeframe: Pharmacokinetic samples were collected predose, just before the end of the infusion, 2, 4, and 8 hours after the start of the infusion.

Maximum measured concentration of the analyte in plasma (Cmax) is presented as adjusted geometric mean (gMean) and geometric coefficient of variation (%) (gCV%). Adjustment was made for treatment effect and weight.

Outcome measures

Outcome measures
Measure	BI 695502 (T) n=30 Participants Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) BI 695502 concentrate for solution for infusion.	United States (US)-Licensed Avastin® (R1) n=30 Participants Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) US-licensed Avastin® solution for intravenous infusion.	European Union (EU)-Approved Avastin® (R2) n=30 Participants Subjects were administered a single dose of 25 microgram per millilitre (mg/mL) EU-approved Avastin® concentrate for solution for infusion.
Maximum Measured Concentration of the Analyte in Plasma (Cmax)	23.783 microgram/milliliter Geometric Coefficient of Variation 16.11	23.425 microgram/milliliter Geometric Coefficient of Variation 25.15	25.505 microgram/milliliter Geometric Coefficient of Variation 15.18

Adverse Events

BI 695502 (T)

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

United States (US)-Licensed Avastin® (R1)

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

European Union (EU)-Approved Avastin® (R2)

Serious events: 0 serious events

Other events: 21 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 695502 (T) n=30 participants at risk Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) BI 695502 concentrate for solution for infusion.	United States (US)-Licensed Avastin® (R1) n=30 participants at risk Subjects were administered a single dose of 25 milligram per millilitre (mg/mL) US-licensed Avastin® solution for intravenous infusion.	European Union (EU)-Approved Avastin® (R2) n=31 participants at risk Subjects were administered a single dose of 25 microgram per millilitre(mg/mL) EU-approved Avastin® concentrate for solution for infusion.
Infections and infestations Upper respiratory tract infection	36.7% 11/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	20.0% 6/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	41.9% 13/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Infections and infestations Respiratory tract infection	10.0% 3/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	3.3% 1/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	0.00% 0/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Infections and infestations Gastroenteritis	6.7% 2/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	0.00% 0/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	3.2% 1/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Infections and infestations Rhinitis	6.7% 2/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	0.00% 0/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	3.2% 1/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Nervous system disorders Headache	30.0% 9/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	20.0% 6/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	12.9% 4/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Nervous system disorders Dizziness	10.0% 3/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	3.3% 1/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	0.00% 0/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Vascular disorders Orthostatic hypotension	0.00% 0/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	6.7% 2/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	0.00% 0/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Gastrointestinal disorders Toothache	6.7% 2/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	6.7% 2/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	3.2% 1/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Gastrointestinal disorders Diarrhoea	3.3% 1/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	3.3% 1/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	6.5% 2/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	0.00% 0/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	6.5% 2/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Gastrointestinal disorders Nausea	0.00% 0/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	3.3% 1/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	6.5% 2/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Musculoskeletal and connective tissue disorders Back pain	10.0% 3/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	0.00% 0/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	3.2% 1/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.7% 2/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	0.00% 0/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	0.00% 0/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	6.7% 2/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	0.00% 0/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Injury, poisoning and procedural complications Thermal burn	3.3% 1/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	10.0% 3/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	0.00% 0/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Injury, poisoning and procedural complications Laceration	0.00% 0/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	3.3% 1/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	9.7% 3/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Injury, poisoning and procedural complications Contusion	6.7% 2/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	6.7% 2/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	0.00% 0/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.
Injury, poisoning and procedural complications Muscle strain	3.3% 1/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	6.7% 2/30 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.	3.2% 1/31 • From first drug administration to end of trial; up to 99 days. Any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a subject in a clinical investigation who received a pharmaceutical product. The recorded Adverse Event may not have had a causal relationship with this treatment.