To investigate the potential of an interaction between 4 mg/kg and 16 mg/kg sugammadex and enoxaparin or UFH on anticoagulant activity in young healthy male volunteers.
ID
Source
Brief title
Condition
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
part 1 - to investigate the potential effect of 4 mg/kg and 16 mg/kg sugammadex
on the Anti-Xa anticoagulant activity of enoxaparin.
part 2 - to investigate the potential effect of 4 mg/kg and 16 mg/kg sugammadex
on the APTT anticoagulant activity of UFH.
Secondary outcome
part 1:
- To investigate the potential effect of 4 mg/kg and 16 mg/kg sugammadex on the
APTT anticoagulant activity of enoxaparin.
- To evaluate the effect of enoxaparin on the potential APTT anticoagulant
activity of 4 mg/kg sugammadex.
- To evaluate the potential anticoagulant activity of 4 mg/kg sugammadex as
compared to baseline. Anti-Xa activity and APTT will be the secondary endpoint
measures.
- To evaluate the safety and tolerability of sugammadex alone or in combination
with enoxaparin.
part 2
- To evaluate the effect of UFH on the potential APTT anticoagulant activity of
16 mg/kg sugammadex.
- To evaluate the potential anticoagulant activity of 16 mg/kg sugammadex as
compared to baseline; APTT and anti-Xa activity will be the secondary endpoint
measures.
- To evaluate the safety and tolerability of sugammadex alone or in combination
with UFH.
Background summary
Sugammadex has been designed to specifically bind rocuronium and vecuronium
with very high affinity. Upon complexation with a neuromuscular blocking agent
(NMBA) such as rocuronium, sugammadex reduces the amount of NMBA available to
bind to nicotinic receptors in the neuromuscular junction, and hence results in
the reversal of neuromuscular blockade (NMB). Sugammadex is approved for use in
humans since September 2008 in the EU under the brand name Bridion®, and is
currently approved in over 60 countries.
The current study will investigate the interaction between sugammadex and
enoxaparin or unfractioned heparin (UFH), as enoxaparin and UFH are frequently
used for the prophylaxis of deep vein thrombosis (DVT) during surgery.
Study objective
To investigate the potential of an interaction between 4 mg/kg and 16 mg/kg
sugammadex and enoxaparin or UFH on anticoagulant activity in young healthy
male volunteers.
Study design
Randomized, double-blind, placebo-controlled, 4 period, 2 part cross-over,
drug-drug interaction study in young healthy male volunteers
Intervention
part 1 - intereractiion sugammadex and enoxaparine: administration of
sugammadex (2x 4 mg/kg, 1x 16 mg/kg, 1x placebo) and enoxaparin (3x 40 mg, 1x
placebo)
part 2 - interaction sugammadex and UFH: administration of sugammadex (1x 4
mg/kg, 2x 16 mg/kg, 1x placebo) and UFH (3x 5000 units, 1x placebo)
Study burden and risks
- Relatively frequent blood collection.
- The insertion of the cannula can be painful and result in a bruise.
- The use of sugammadex could influence coagualation and may uncommonly cause a
hypersensitivity reaction.
- Enoxaparin and UFH may reduce blood coagulation and therefore may cause
bruises. In addition, liver function may be transiently affected or an
injection side reaction may occur.
2015 Galloping Hill Road
Kenilworth, NJ 07033
US
2015 Galloping Hill Road
Kenilworth, NJ 07033
US
Listed location countries
Age
Inclusion criteria
- Healthy male volunteers
- 18-45 years of age
- BMI 18-32
- Subjects must be free of any clinical significant disease that would interfere with the study evaluations.
- No clinically significant abnormalities in laboratory tests (chemistry, hematology, virology, urinalysis)
- APTT and PT within normal limits and anti-Xa activity below LLOQ
- Normal physical examination (including vital sign measurements), normal ECG
Exclusion criteria
- Subject's female partner is pregnant, intends to become pregnant (within 3 months of ending the study), or is breastfeeding
- Subject who will not be able to participate optimally in the study
- Contraindications to heparin or enoxaparin or history of heparin induced thrombocytopenia
- A (suspected) history of hypersensitivity or hypersensitivity-like reaction to sugammadex, history of sensitivity/idiosyncrasy to chemically related compounds or excipients which could be employed in the study or to any other unknown drug used in the past
- Subject is not able to refrain from alcohol, grapefruit, xanthines as described in protocol
- Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug
- History of infectious disease during past month that in the opinion of the investigator, affects subject's ability to participate in the study
- History of an unexplained reaction or hypersensitivity reaction during previous surgery and/or anesthesia
- Subject who underwent surgery during past year
- History of anaphylaxis from any cause, a suspected history of hypersensitivity reactions to cyclodextrins, or multiple drug hypersensitivities
- History of allergic reactions (eg, food, drug, atopic reactions or asthmatic episodes) which, in the opinion of the investigator, interfere with their ability to participate in the study
- Positive screen for drugs or alcohol
- Drug or alcohol abuse in the past 2 years
- Smoking more than 10 cigarettes or equivalent tobacco use per day
- Clinically significant abnormalities in laboratory tests (chemistry, hematology, virology, coagulation) or physical examination
- Subjects with hereditary vitamin K dependent clotting factor deficiencies and/or pre-existing coagulopathies
- History of gastrointestinal bleeding, easy bruising, frequent nose bleeds
- Previous exposure to sugammadex
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-001969-41-NL |
| CCMO | NL37049.058.11 |