Protocol for Phase IIb Study of YM150. A Randomized, Double-Blind, Double-Dummy, Parallel Group Study to Compare YM150 bid and qd Doses and Enoxaparin for Prevention of Venous Thromboembolism in Subjects Undergoing Elective Hip Replacement Surgery. A Phase IIb study to Evaluate the Efficacy and Safety of YM150 Compared to Enoxaparin in Subjects undergoing Elective Hip Replacement Surgery. - ONYX-3

• Register: EUCTR
• Last refreshed on: 12 June 2012
• Main ID: EUCTR2008-004416-13-GB
• Date of registration: 09/04/2009
• Prospective Registration: Yes
• Primary sponsor: Astellas Pharma Europe B.V.
• Public title: Protocol for Phase IIb Study of YM150. A Randomized, Double-Blind, Double-Dummy, Parallel Group Study to Compare YM150 bid and qd Doses and Enoxaparin for Prevention of Venous Thromboembolism in Subjects Undergoing Elective Hip Replacement Surgery. A Phase IIb study to Evaluate the Efficacy and Safety of YM150 Compared to Enoxaparin in Subjects undergoing Elective Hip Replacement Surgery. - ONYX-3
• Scientific title: Protocol for Phase IIb Study of YM150. A Randomized, Double-Blind, Double-Dummy, Parallel Group Study to Compare YM150 bid and qd Doses and Enoxaparin for Prevention of Venous Thromboembolism in Subjects Undergoing Elective Hip Replacement Surgery. A Phase IIb study to Evaluate the Efficacy and Safety of YM150 Compared to Enoxaparin in Subjects undergoing Elective Hip Replacement Surgery. - ONYX-3
• Date of first enrolment: 22/07/2009
• Target sample size: 2000
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004416-13
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Double dummy If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Austria, Czech Republic, Denmark, Estonia, Finland, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Slovakia, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subject is eligible for the study if all of the following apply:
1. Written informed consent [and Healthcare Insurance Portability and Accountability Act (HIPAA) Authorization for U.S. sites only] has been obtained before screening.
2. Male or female subject aged 18 years or older.
3. Subject is scheduled for elective hip replacement surgery.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Subject will be excluded from participation if any of the following applies:
1. Female subject of childbearing potential who refuses to use a medically acceptable form of contraception throughout the study. (Acceptable methods of contraception are: oral or injectable hormonal contraceptives and intrauterine devices. Male study subjects should be advised to use male condom in addition to having their partner use another acceptable method during the study and for three months after the last dose.)
2. Female subject who is pregnant or lactating, or has a positive pregnancy test within 72 hours prior to randomization.
3. Subject has active bleeding or any condition associated with increased risk of bleeding including known hemorrhagic disorder or thrombocytopenia (platelet count <100,000/mm3) at screening.
4. Subject has had an MI or stroke within 3 months before planned hip replacement surgery.
5. Subject has persistent blood pressure (BP) of 160 mmHg systolic or higher and/or 100 mmHg diastolic or higher at baseline with or without medication.
6. Subject has any concurrent illness, which, in the opinion of the investigator, may interfere with treatment or evaluation of safety or completion of this study.
7. Subject has had major trauma or major surgery; or eye, spinal cord or brain surgery within 3 months before planned hip replacement surgery.
8. Subject requires scheduled major surgery or other invasive procedures with potential for uncontrolled bleeding during the study.
9. Subject requires use of prohibited concomitant medication (e.g. anticoagulants such as heparins, thrombin inhibitors, coumarins, or acetylsalicylic acid use of >163 mg/day) at any time during the period extending from one week before the start of study drug until the end of the treatment period of 35 days.
10. Subject has hypersensitivity or any contraindications to iodinated contrast medium or enoxaparin.
11. Subject has planned indwelling intrathecal or epidural catheter for more than 6 hours after the end of surgery.
12. Subject has a creatinine clearance of <60 mL/min, as calculated by the Cockcroft-Gault equation (see Appendix 1) at screening.
13. Subject has hepatic insufficiency or presents with AST or ALT > 2 times or total bilirubin > 1.5 times ULN at screening.
14. Subject has a lower extremity amputation (toe(s) amputation only is acceptable).
15. Subject is scheduled for simultaneous bilateral hip replacement surgery.
16. Subject has participated in another clinical trial of an investigational drug (including placebo) or device within 30 days (or the limit set by national law, whichever is longer) of signing of informed consent for the present study.
17. Subject has previously participated in a clinical trial with YM150.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Prevention of venous thromboembolism after hip replacement surgery.
MedDRA version: 9.1 Level: LLT Classification code 10043634 Term: Thrombosis prophylaxis

Intervention(s)

Product Name: YM150
Product Code: YM150
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: YM150
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: YM150
Product Code: YM150
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: YM150
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: YM150
Product Code: YM150
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: YM150
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Lovenox
Pharmaceutical Form: Injection*
INN or Proposed INN: enoxaparin sodium
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 40mg/0.4ml-
Pharmaceutical form of the placebo: Injection*
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: *To characterize PK of the active metabolite YM-222714, in subjects undergoing elective hip replacement surgery.
*To characterize PK/Coagulation parameters relationship, in subjects undergoing elective hip replacement surgery.
*To evaluate the effects of YM150 and enoxaparin on:
- The health status of subjects undergoing elective hip replacement surgery,
- The health care resource use associated with both treatment options, and
- The cost-effectiveness associated with both treatment options.

Main Objective: The primary objective is to evaluate the efficacy and safety of 15 mg bid, 30 mg qd, 30 mg bid and 60 mg qd YM150 and to compare efficacy and safety with enoxaparin 40 mg qd, in subjects undergoing elective hip replacement surgery.

Primary end point(s): The primary efficacy variable is the composite of the following adjudicated events observed until day 12:
• Proximal or distal DVT
• Symptomatic DVT (proximal and distal)
• Non-fatal PE
• Death from all causes

Secondary ID(s)

150-CL-040

2008-004416-13-AT