Pharmacokinetic, Safety, Tolerability and Immunogenicity Study of SB3 in Healthy Male Subjects

• Sponsor: Samsung Bioepis Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02075073
• Collaborator: (none)
• Enrollment: 109
• Location: 1
• Arms: 3
• Duration (Months): 1.9
• Patients Per Site Per Month: 56.2

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the pharmacokinetics, safety, tolerability and immunogenicity of SB3 and Herceptin® (EU sourced Herceptin® and US sourced Herceptin®) in healthy male subjects.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Biological: SB3; Biological: EU sourced Herceptin®; Biological: US sourced Herceptin®	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 109 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: A Randomised, Double-blind, Three-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics, Safety, Tolerability, and Immunogenicity of Three Formulations of Trastuzumab (SB3, EU Sourced Herceptin® and US Sourced Herceptin®) in Healthy Male Subjects
• Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SB3 SB3, single dose of 6 mg/kg via intravenous infusion (study drug)	Biological: SB3
Active Comparator: EU sourced Herceptin® EU sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug)	Biological: EU sourced Herceptin®
Active Comparator: US sourced Herceptin® US sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug)	Biological: US sourced Herceptin®

Outcome Measures

Primary Outcome Measures

1. Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) [57 days]

2. Maximum Serum Concentration (Cmax) [57 days]

3. Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) [57 days]

Secondary Outcome Measures

1. Time to Cmax (Tmax) [57 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy male subjects

• Have a body weight between 60.0 and 94.9 kg and a body mass index between 18.0 and 29.9 kg/m², inclusive.

Exclusion Criteria:

• history of and/or current clinically significant gastrointestinal, renal, hepatic, cardiovascular, haematological (including pancytopenia, aplastic anaemia or blood dyscrasia), pulmonary, neurologic, metabolic (including known diabetes mellitus), psychiatric or significant allergic disease excluding mild asymptomatic allergies.

• history of and/or current cardiac disease

• previously received any monoclonal antibody or fusion protein.

• history of cancer including lymphoma, leukaemia and skin cancer.

• Have received live vaccine(s) within 30 days prior to Screening or who will require a vaccine(s) between Screening and the End of Study visit.

• intake medication with a half-life > 24 h within 1 month or 10 half-lives of the medication prior to the administration of investigational product.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Samsung Investigational Site	Berlin		Germany

Sponsors and Collaborators

• Samsung Bioepis Co., Ltd.

Investigators

• Study Director: Saumsung Bioepis, Samsung Bioepis Co., Ltd.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Samsung Bioepis Co., Ltd.
• ClinicalTrials.gov Identifier: NCT02075073
• Other Study ID Numbers: SB3-G11-NHV; 2013-004112-21
• First Posted: Mar 3, 2014
• Last Update Posted: Sep 14, 2017
• Last Verified: Aug 1, 2017

• Keywords provided by Samsung Bioepis Co., Ltd.: Pharmacokinetics
• Additional relevant MeSH terms: Trastuzumab

Study Results

Participant Flow

Arm/Group Title	SB3 (Proposed Trastuzumab Biosimilar)	EU Sourced Herceptin®	US Sourced Herceptin®
Arm/Group Description	SB3, single dose of 6 mg/kg via intravenous infusion (study drug) SB3	EU sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) EU sourced Herceptin®	US sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) US sourced Herceptin®
Period Title: Overall Study
STARTED	36	37	36
COMPLETED	36	36	36
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	SB3 (Proposed Trastuzumab Biosimilar)	EU Sourced Herceptin®	US Sourced Herceptin®	Total
Arm/Group Description	SB3, single dose of 6 mg/kg via intravenous infusion (study drug) SB3	EU sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) EU sourced Herceptin®	US sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) US sourced Herceptin®	Total of all reporting groups
Overall Participants	36	37	36	109
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.4 (10.29)	39.3 (10.80)	38.7 (11.40)	38.8 (10.75)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%
Male	36 100%	37 100%	36 100%	109 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf)
Time Frame	57 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SB3 (Proposed Trastuzumab Biosimilar)	EU Sourced Herceptin®	US Sourced Herceptin®
Arm/Group Description	SB3, single dose of 6 mg/kg via intravenous infusion (study drug) SB3	EU sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) EU sourced Herceptin®	US sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) US sourced Herceptin®
Measure Participants	36	36	36
Mean (Standard Deviation) [µg·h/mL]	34783.4 (5614.13)	35889.9 (5761.37)	37370.3 (5620.05)

2. Primary Outcome

Title	Maximum Serum Concentration (Cmax)
Time Frame	57 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SB3 (Proposed Trastuzumab Biosimilar)	EU Sourced Herceptin®	US Sourced Herceptin®
Arm/Group Description	SB3, single dose of 6 mg/kg via intravenous infusion (study drug) SB3	EU sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) EU sourced Herceptin®	US sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) US sourced Herceptin®
Measure Participants	36	36	36
Mean (Standard Deviation) [µg/mL]	154.224 (28.0068)	153.479 (24.7249)	155.513 (25.5812)

3. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast)
Time Frame	57 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SB3 (Proposed Trastuzumab Biosimilar)	EU Sourced Herceptin®	US Sourced Herceptin®
Arm/Group Description	SB3, single dose of 6 mg/kg via intravenous infusion (study drug) SB3	EU sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) EU sourced Herceptin®	US sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) US sourced Herceptin®
Measure Participants	36	36	36
Mean (Standard Deviation) [µg·h/mL]	34320.8 (5349.12)	35367.5 (5524.09)	36690.4 (5341.68)

4. Secondary Outcome

Title	Time to Cmax (Tmax)
Time Frame	57 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	SB3 (Proposed Trastuzumab Biosimilar)	EU Sourced Herceptin®	US Sourced Herceptin®
Arm/Group Description	SB3, single dose of 6 mg/kg via intravenous infusion (study drug) SB3	EU sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) EU sourced Herceptin®	US sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) US sourced Herceptin®
Measure Participants	36	36	36
Mean (Standard Deviation) [hour]	4.691 (15.6597)	3.529 (7.6948)	2.799 (3.7569)

Adverse Events

Arm/Group Title	SB3 (Proposed Trastuzumab Biosimilar)		EU Sourced Herceptin®		US Sourced Herceptin®
Arm/Group Description	SB3, single dose of 6 mg/kg via intravenous infusion (study drug) SB3		EU sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) EU sourced Herceptin®		US sourced Herceptin®, single dose of 6 mg/kg via intravenous infusion (reference drug) US sourced Herceptin®
All Cause Mortality
	SB3 (Proposed Trastuzumab Biosimilar)		EU Sourced Herceptin®		US Sourced Herceptin®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/36 (0%)		0/36 (0%)
Serious Adverse Events
	SB3 (Proposed Trastuzumab Biosimilar)		EU Sourced Herceptin®		US Sourced Herceptin®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/36 (2.8%)		0/36 (0%)		0/36 (0%)
Musculoskeletal and connective tissue disorders
Chondropathy	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Other (Not Including Serious) Adverse Events
	SB3 (Proposed Trastuzumab Biosimilar)		EU Sourced Herceptin®		US Sourced Herceptin®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/36 (69.4%)		23/36 (63.9%)		25/36 (69.4%)
Cardiac disorders
Tachycardia	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Atrial fibrillation	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Palpitations	0/36 (0%)	0	1/36 (2.8%)	1	1/36 (2.8%)	3
Ear and labyrinth disorders
Ear pain	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Eye disorders
Dry eye	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Ocular hyperaemia	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Vision blurred	0/36 (0%)	0	0/36 (0%)	0	2/36 (5.6%)	2
Gastrointestinal disorders
Diarrhoea	2/36 (5.6%)	3	1/36 (2.8%)	1	1/36 (2.8%)	1
Toothache	1/36 (2.8%)	1	2/36 (5.6%)	2	0/36 (0%)	0
Nausea	1/36 (2.8%)	1	1/36 (2.8%)	1	0/36 (0%)	0
Gastric disorder	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Abdominal discomfort	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Proctalgia	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
General disorders
Fatigue	3/36 (8.3%)	4	1/36 (2.8%)	1	3/36 (8.3%)	3
Chills	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Pyrexia	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Infections and infestations
Nasopharyngitis	4/36 (11.1%)	4	4/36 (11.1%)	4	8/36 (22.2%)	8
Upper respiratory tract infection	2/36 (5.6%)	2	1/36 (2.8%)	1	0/36 (0%)	0
Rhinitis	2/36 (5.6%)	3	0/36 (0%)	0	2/36 (5.6%)	2
Oral herpes	2/36 (5.6%)	2	3/36 (8.3%)	3	2/36 (5.6%)	2
Viral infection	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Hordeolum	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Herpes simplex	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Injury, poisoning and procedural complications
Infusion related reaction	9/36 (25%)	9	8/36 (22.2%)	8	16/36 (44.4%)	16
Ankle fracture	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Joint injury	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Musculoskeletal and connective tissue disorders
Myalgia	3/36 (8.3%)	3	0/36 (0%)	0	1/36 (2.8%)	1
Back pain	2/36 (5.6%)	2	0/36 (0%)	0	3/36 (8.3%)	3
Chondropathy	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Pain in extremity	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Arthralgia	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Muscle spasms	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Nervous system disorders
Headache	9/36 (25%)	12	4/36 (11.1%)	4	5/36 (13.9%)	5
Dizziness	2/36 (5.6%)	2	0/36 (0%)	0	0/36 (0%)	0
Disturbance in attention	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Sciatica	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Syncope	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Somnolence	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Psychiatric disorders
Affect lability	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	4/36 (11.1%)	6	0/36 (0%)	0	0/36 (0%)	0
Oropharyngeal pain	1/36 (2.8%)	1	1/36 (2.8%)	1	1/36 (2.8%)	1
Cough	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Nasal congestion	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Nasal discomfort	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Skin and subcutaneous tissue disorders
Dermatitis acneiform	1/36 (2.8%)	1	1/36 (2.8%)	1	0/36 (0%)	0
Rash macular	1/36 (2.8%)	1	0/36 (0%)	0	1/36 (2.8%)	1
Skin irritation	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Acne	0/36 (0%)	0	1/36 (2.8%)	1	2/36 (5.6%)	2
Dry skin	0/36 (0%)	0	1/36 (2.8%)	1	1/36 (2.8%)	1
Erythema	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Night sweats	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Rash	0/36 (0%)	0	1/36 (2.8%)	1	3/36 (8.3%)	3
Hyperhidrosis	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Vascular disorders
Haematoma	1/36 (2.8%)	1	1/36 (2.8%)	1	0/36 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Project results may not be published or referred to, in whole or in part, by the Service Provider or any of its Affiliates without the prior expressed written consent of Sponsor, which will not be unreasonably withheld or delayed. Neither Party shall use the other Party's name in connection with any publication or promotion without the other Party's prior written consent.