Trial Outcomes & Findings for Trial to Assess the Safety of Vorapaxar in Japanese Subjects With Cerebral Infarction (P05005; MK-5348-017) (NCT NCT00684515)
NCT ID: NCT00684515
Last Updated: 2018-09-21
Results Overview
An adverse event (AE) is any unfavorable and unintended change in the structure, function, or chemistry of the body temporarily associated with study drug administration, whether or not considered related to study drug. MACE events were defined as nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization due to recurrent ischemia, or urgent coronary revascularization. All MACE events were excluded from this analysis.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
90 participants
Primary outcome timeframe
Up to Day 121
Results posted on
2018-09-21
Participant Flow
Participant milestones
| Measure |
Vorapaxar 1 mg
Vorapaxar 1 mg tablets administered orally once daily for 60 days.
|
Vorapaxar 2.5 mg
Vorapaxar 2.5 mg tablets administered orally once daily for 60 days.
|
Placebo
Matching placbo tablets to Vorapaxar administered orally once daily for 60 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
33
|
29
|
28
|
|
Overall Study
COMPLETED
|
29
|
26
|
27
|
|
Overall Study
NOT COMPLETED
|
4
|
3
|
1
|
Reasons for withdrawal
| Measure |
Vorapaxar 1 mg
Vorapaxar 1 mg tablets administered orally once daily for 60 days.
|
Vorapaxar 2.5 mg
Vorapaxar 2.5 mg tablets administered orally once daily for 60 days.
|
Placebo
Matching placbo tablets to Vorapaxar administered orally once daily for 60 days.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
3
|
1
|
|
Overall Study
Protocol-Defined Clinical Event
|
1
|
0
|
0
|
Baseline Characteristics
Trial to Assess the Safety of Vorapaxar in Japanese Subjects With Cerebral Infarction (P05005; MK-5348-017)
Baseline characteristics by cohort
| Measure |
Vorapaxar 1 mg
n=33 Participants
Vorapaxar 1 mg tablets administered orally once daily for 60 days.
|
Vorapaxar 2.5 mg
n=29 Participants
Vorapaxar 2.5 mg tablets administered orally once daily for 60 days.
|
Placebo
n=28 Participants
Matching placbo tablets to Vorapaxar administered orally once daily for 60 days.
|
Total
n=90 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
63.0 Years
STANDARD_DEVIATION 10.0 • n=93 Participants
|
65.8 Years
STANDARD_DEVIATION 11.6 • n=4 Participants
|
63.7 Years
STANDARD_DEVIATION 8.9 • n=27 Participants
|
64.3 Years
STANDARD_DEVIATION 10.8 • n=483 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
21 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
23 Participants
n=27 Participants
|
69 Participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Up to Day 121Population: The population consisted of all enrolled participants that received at least one dose of study drug.
An adverse event (AE) is any unfavorable and unintended change in the structure, function, or chemistry of the body temporarily associated with study drug administration, whether or not considered related to study drug. MACE events were defined as nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization due to recurrent ischemia, or urgent coronary revascularization. All MACE events were excluded from this analysis.
Outcome measures
| Measure |
Vorapaxar 1 mg
n=33 Participants
Vorapaxar 1 mg tablets administered orally once daily for 60 days.
|
Vorapaxar 2.5 mg
n=29 Participants
Vorapaxar 2.5 mg tablets administered orally once daily for 60 days.
|
Placebo
n=28 Participants
Matching placbo tablets to Vorapaxar administered orally once daily for 60 days.
|
|---|---|---|---|
|
Number of Participants Experiencing Non-Major Adverse Cardiac Events (Non-MACE)
|
27 Participants
|
27 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: Up to Day 60Population: The population consisted of all enrolled participants that received at least one dose of study drug and had TIMI bleeding data available.
Major TIMI bleeding was defined as any intracranial bleeding (excluding micohemorrhages \<10 mm evident on magnetic resonance imaging \[MRI\]), clinical over signs of hemorrhge associated with a drop in hemoglobin \>=5 g/dL, or fatal bleeding (bleeding that directly results in death within 7 days). Minor TIMI bleeding was defined as any clinically overt bleeding resulting in a hemoglobin drop of 3 to \<5 g/dL. Non-TIMI bleeding included all bleeding events not covered under Major TIMI or Minor TIMI bleeding.
Outcome measures
| Measure |
Vorapaxar 1 mg
n=33 Participants
Vorapaxar 1 mg tablets administered orally once daily for 60 days.
|
Vorapaxar 2.5 mg
n=29 Participants
Vorapaxar 2.5 mg tablets administered orally once daily for 60 days.
|
Placebo
n=28 Participants
Matching placbo tablets to Vorapaxar administered orally once daily for 60 days.
|
|---|---|---|---|
|
Number of Paticipants Experiencing Thrombolysis in Myocardial Infarction (TIMI) Major, Minor, and Non-TIMI Bleeding Events
Major TIMI Bleeding
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Paticipants Experiencing Thrombolysis in Myocardial Infarction (TIMI) Major, Minor, and Non-TIMI Bleeding Events
Minor TIMI Bleeding
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Paticipants Experiencing Thrombolysis in Myocardial Infarction (TIMI) Major, Minor, and Non-TIMI Bleeding Events
Non-TIMI Bleeding
|
5 Participants
|
10 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Up to Day 121Population: The population consisted of all enrolled participants that received at least one dose of study drug.
The number of participants experiencing major cardiac events or death was evaluated up to Day 121. Major cardiac events were defined as nonfatal stroke, hospitalization due to recurrent ischemia, or urgent coronary revascularization.
Outcome measures
| Measure |
Vorapaxar 1 mg
n=33 Participants
Vorapaxar 1 mg tablets administered orally once daily for 60 days.
|
Vorapaxar 2.5 mg
n=29 Participants
Vorapaxar 2.5 mg tablets administered orally once daily for 60 days.
|
Placebo
n=28 Participants
Matching placbo tablets to Vorapaxar administered orally once daily for 60 days.
|
|---|---|---|---|
|
Number of Participants With MACE or Death
MACE
|
1 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With MACE or Death
Death
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Up to Day 60Population: The population consisted of all enrolled participants who received at least one dose of study drug and had hs-CRP data available.
Participant blood samples were collected to determine the median serum level of hs-CRP. hs-cRP levels reflect the underlying level of inflammation. The higher the level, the greater the disease burden.
Outcome measures
| Measure |
Vorapaxar 1 mg
n=33 Participants
Vorapaxar 1 mg tablets administered orally once daily for 60 days.
|
Vorapaxar 2.5 mg
n=29 Participants
Vorapaxar 2.5 mg tablets administered orally once daily for 60 days.
|
Placebo
n=28 Participants
Matching placbo tablets to Vorapaxar administered orally once daily for 60 days.
|
|---|---|---|---|
|
Median High-Sensitivity C-Reactive Protein (Hs-CRP) Levels By Study Visit
Day 7 (n=32, 28, 27)
|
0.77 mg/L
Standard Deviation 2.33
|
0.49 mg/L
Standard Deviation 0.73
|
0.41 mg/L
Standard Deviation 0.58
|
|
Median High-Sensitivity C-Reactive Protein (Hs-CRP) Levels By Study Visit
Baseline (n=33, 29, 28)
|
0.65 mg/L
Standard Deviation 1.44
|
0.67 mg/L
Standard Deviation 1.66
|
0.56 mg/L
Standard Deviation 1.06
|
|
Median High-Sensitivity C-Reactive Protein (Hs-CRP) Levels By Study Visit
Day 14 (32, 29, 28)
|
0.93 mg/L
Standard Deviation 2.69
|
0.62 mg/L
Standard Deviation 0.79
|
0.44 mg/L
Standard Deviation 0.72
|
|
Median High-Sensitivity C-Reactive Protein (Hs-CRP) Levels By Study Visit
Day 30 (n=31, 28, 28)
|
0.96 mg/L
Standard Deviation 3.95
|
0.55 mg/L
Standard Deviation 1.07
|
0.56 mg/L
Standard Deviation 0.95
|
|
Median High-Sensitivity C-Reactive Protein (Hs-CRP) Levels By Study Visit
Day 45 (n=29, 27, 28)
|
0.70 mg/L
Standard Deviation 1.09
|
0.48 mg/L
Standard Deviation 0.74
|
0.59 mg/L
Standard Deviation 0.76
|
|
Median High-Sensitivity C-Reactive Protein (Hs-CRP) Levels By Study Visit
Day 60 (n=29, 26, 27)
|
0.59 mg/L
Standard Deviation 0.58
|
0.53 mg/L
Standard Deviation 0.63
|
0.61 mg/L
Standard Deviation 0.93
|
SECONDARY outcome
Timeframe: Up to Day 60Population: The population consisted of all enrolled participants that received at least one dose of study drug and had CD40 ligand data available.
Participant blood samples were collected to determine the mean serum level of CD40 ligand. CD40 ligand values represent the level of disease activation with a higher level of CD40 ligand indicating a greater underlying risk.
Outcome measures
| Measure |
Vorapaxar 1 mg
n=33 Participants
Vorapaxar 1 mg tablets administered orally once daily for 60 days.
|
Vorapaxar 2.5 mg
n=29 Participants
Vorapaxar 2.5 mg tablets administered orally once daily for 60 days.
|
Placebo
n=28 Participants
Matching placbo tablets to Vorapaxar administered orally once daily for 60 days.
|
|---|---|---|---|
|
Mean CD40 Ligand Levels By Study Visit
Day 14 (n=32, 29, 28)
|
6.3 mg/L
Standard Error 0.64
|
6.5 mg/L
Standard Error 0.79
|
6.6 mg/L
Standard Error 0.66
|
|
Mean CD40 Ligand Levels By Study Visit
Day 60 (n=29, 26, 27)
|
6.2 mg/L
Standard Error 0.82
|
5.3 mg/L
Standard Error 0.76
|
6.0 mg/L
Standard Error 0.56
|
|
Mean CD40 Ligand Levels By Study Visit
Baseline (n=33, 29, 28)
|
6.5 mg/L
Standard Error 0.62
|
8.3 mg/L
Standard Error 0.77
|
5.9 mg/L
Standard Error 0.62
|
|
Mean CD40 Ligand Levels By Study Visit
Day 7 (n=32, 28, 27)
|
7.2 mg/L
Standard Error 0.71
|
5.8 mg/L
Standard Error 0.74
|
5.6 mg/L
Standard Error 0.60
|
|
Mean CD40 Ligand Levels By Study Visit
Day 30 (n=31, 28, 28)
|
6.7 mg/L
Standard Error 0.79
|
7.1 mg/L
Standard Error 0.78
|
5.9 mg/L
Standard Error 0.60
|
|
Mean CD40 Ligand Levels By Study Visit
Day 45 (n=29, 27, 28)
|
5.9 mg/L
Standard Error 0.77
|
5.7 mg/L
Standard Error 0.77
|
6.2 mg/L
Standard Error 0.54
|
SECONDARY outcome
Timeframe: Up to Day 60Population: The population consisted of all enrolled participants that received at least one dose of study drug and had membrane-bound p-selectin data available.
Participant blood samples were collected at Baseline, Day 30, and Day 60 to determine the mean level of membrane-bound p-selectin in the serum. Membrane-bound P-selectin levels reflect the underlying level of inflammation. Intensity levels are reported in arbitrary units 0 (dark) to 1023 (bright). Higher values correspond to greater membrane-bound P-Selectin levels.
Outcome measures
| Measure |
Vorapaxar 1 mg
n=2 Participants
Vorapaxar 1 mg tablets administered orally once daily for 60 days.
|
Vorapaxar 2.5 mg
n=1 Participants
Vorapaxar 2.5 mg tablets administered orally once daily for 60 days.
|
Placebo
n=3 Participants
Matching placbo tablets to Vorapaxar administered orally once daily for 60 days.
|
|---|---|---|---|
|
Mean Membrane-Bound P-Selectin Levels By Study Visit
Baseline (n=2, 1, 3)
|
15.7 Arbitrary Units
Standard Error 0.80
|
19.5 Arbitrary Units
Standard Error NA
Due to the sample size of 1 participant, calculation of the SE was not possible.
|
17.4 Arbitrary Units
Standard Error 1.06
|
|
Mean Membrane-Bound P-Selectin Levels By Study Visit
Day 30 (n=2, 1, 3)
|
19.9 Arbitrary Units
Standard Error 4.20
|
16.6 Arbitrary Units
Standard Error NA
Due to the sample size of 1 participant, calculation of the SE was not possible.
|
17.1 Arbitrary Units
Standard Error 1.10
|
|
Mean Membrane-Bound P-Selectin Levels By Study Visit
Day 60 (n=2, 1, 3)
|
17.8 Arbitrary Units
Standard Error 0.05
|
18.3 Arbitrary Units
Standard Error NA
Due to the sample size of 1 participant, calculation of the SE was not possible.
|
18.0 Arbitrary Units
Standard Error 0.07
|
Adverse Events
Vorapaxar 1 mg
Serious events: 1 serious events
Other events: 26 other events
Deaths: 0 deaths
Vorapaxar 2.5 mg
Serious events: 2 serious events
Other events: 24 other events
Deaths: 0 deaths
Placebo
Serious events: 3 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Vorapaxar 1 mg
n=33 participants at risk
Vorapaxar 1 mg tablets administered orally once daily for 60 days.
|
Vorapaxar 2.5 mg
n=29 participants at risk
Vorapaxar 2.5 mg tablets administered orally once daily for 60 days.
|
Placebo
n=28 participants at risk
Matching placbo tablets to Vorapaxar administered orally once daily for 60 days.
|
|---|---|---|---|
|
Cardiac disorders
Arterial Fibrillation
|
0.00%
0/33 • Up to Day 121
|
3.4%
1/29 • Number of events 1 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/33 • Up to Day 121
|
0.00%
0/29 • Up to Day 121
|
3.6%
1/28 • Number of events 1 • Up to Day 121
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/33 • Up to Day 121
|
3.4%
1/29 • Number of events 1 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal Carcinoma
|
3.0%
1/33 • Number of events 1 • Up to Day 121
|
0.00%
0/29 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Nervous system disorders
Cerebellar Infarction
|
0.00%
0/33 • Up to Day 121
|
0.00%
0/29 • Up to Day 121
|
3.6%
1/28 • Number of events 1 • Up to Day 121
|
|
Respiratory, thoracic and mediastinal disorders
Hyperventilation
|
0.00%
0/33 • Up to Day 121
|
0.00%
0/29 • Up to Day 121
|
3.6%
1/28 • Number of events 1 • Up to Day 121
|
Other adverse events
| Measure |
Vorapaxar 1 mg
n=33 participants at risk
Vorapaxar 1 mg tablets administered orally once daily for 60 days.
|
Vorapaxar 2.5 mg
n=29 participants at risk
Vorapaxar 2.5 mg tablets administered orally once daily for 60 days.
|
Placebo
n=28 participants at risk
Matching placbo tablets to Vorapaxar administered orally once daily for 60 days.
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Haemorrhagic Diathesis
|
3.0%
1/33 • Number of events 1 • Up to Day 121
|
3.4%
1/29 • Number of events 1 • Up to Day 121
|
7.1%
2/28 • Number of events 2 • Up to Day 121
|
|
Cardiac disorders
Supraventricular Extrasystoles
|
6.1%
2/33 • Number of events 3 • Up to Day 121
|
0.00%
0/29 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
6.1%
2/33 • Number of events 2 • Up to Day 121
|
3.4%
1/29 • Number of events 1 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Gastrointestinal disorders
Constipation
|
6.1%
2/33 • Number of events 2 • Up to Day 121
|
3.4%
1/29 • Number of events 1 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
General disorders
Facial Pain
|
0.00%
0/33 • Up to Day 121
|
0.00%
0/29 • Up to Day 121
|
7.1%
2/28 • Number of events 2 • Up to Day 121
|
|
General disorders
Feeling Abnormal
|
3.0%
1/33 • Number of events 1 • Up to Day 121
|
6.9%
2/29 • Number of events 3 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Infections and infestations
Herpes Zoster
|
0.00%
0/33 • Up to Day 121
|
6.9%
2/29 • Number of events 2 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Infections and infestations
Nasopharyngitis
|
24.2%
8/33 • Number of events 9 • Up to Day 121
|
31.0%
9/29 • Number of events 9 • Up to Day 121
|
3.6%
1/28 • Number of events 2 • Up to Day 121
|
|
Injury, poisoning and procedural complications
Subcutaneous Haematoma
|
0.00%
0/33 • Up to Day 121
|
6.9%
2/29 • Number of events 2 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Investigations
Blood Creatine Phosphokinase Increased
|
15.2%
5/33 • Number of events 5 • Up to Day 121
|
6.9%
2/29 • Number of events 3 • Up to Day 121
|
14.3%
4/28 • Number of events 4 • Up to Day 121
|
|
Investigations
Blood Glucose Increased
|
3.0%
1/33 • Number of events 2 • Up to Day 121
|
10.3%
3/29 • Number of events 3 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Investigations
Blood Potassium Increased
|
0.00%
0/33 • Up to Day 121
|
0.00%
0/29 • Up to Day 121
|
7.1%
2/28 • Number of events 2 • Up to Day 121
|
|
Investigations
Blood Triglycerides Increased
|
3.0%
1/33 • Number of events 1 • Up to Day 121
|
6.9%
2/29 • Number of events 2 • Up to Day 121
|
3.6%
1/28 • Number of events 1 • Up to Day 121
|
|
Investigations
Blood Urine Present
|
3.0%
1/33 • Number of events 1 • Up to Day 121
|
10.3%
3/29 • Number of events 3 • Up to Day 121
|
7.1%
2/28 • Number of events 2 • Up to Day 121
|
|
Investigations
Electrocardiogram QT Prolonged
|
3.0%
1/33 • Number of events 1 • Up to Day 121
|
6.9%
2/29 • Number of events 2 • Up to Day 121
|
3.6%
1/28 • Number of events 1 • Up to Day 121
|
|
Investigations
Occult Blood Positive
|
33.3%
11/33 • Number of events 12 • Up to Day 121
|
34.5%
10/29 • Number of events 10 • Up to Day 121
|
25.0%
7/28 • Number of events 7 • Up to Day 121
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
3.0%
1/33 • Number of events 1 • Up to Day 121
|
6.9%
2/29 • Number of events 2 • Up to Day 121
|
3.6%
1/28 • Number of events 1 • Up to Day 121
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/33 • Up to Day 121
|
6.9%
2/29 • Number of events 3 • Up to Day 121
|
3.6%
1/28 • Number of events 1 • Up to Day 121
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness
|
3.0%
1/33 • Number of events 1 • Up to Day 121
|
3.4%
1/29 • Number of events 1 • Up to Day 121
|
7.1%
2/28 • Number of events 2 • Up to Day 121
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
6.1%
2/33 • Number of events 2 • Up to Day 121
|
6.9%
2/29 • Number of events 3 • Up to Day 121
|
7.1%
2/28 • Number of events 2 • Up to Day 121
|
|
Musculoskeletal and connective tissue disorders
Pain in Extremity
|
9.1%
3/33 • Number of events 3 • Up to Day 121
|
3.4%
1/29 • Number of events 1 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Musculoskeletal and connective tissue disorders
Periarthritis
|
0.00%
0/33 • Up to Day 121
|
3.4%
1/29 • Number of events 1 • Up to Day 121
|
10.7%
3/28 • Number of events 3 • Up to Day 121
|
|
Nervous system disorders
Cerebral Infarction
|
3.0%
1/33 • Number of events 2 • Up to Day 121
|
3.4%
1/29 • Number of events 1 • Up to Day 121
|
7.1%
2/28 • Number of events 2 • Up to Day 121
|
|
Nervous system disorders
Cervicobrachial Syndrome
|
6.1%
2/33 • Number of events 2 • Up to Day 121
|
0.00%
0/29 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Nervous system disorders
Dizziness
|
6.1%
2/33 • Number of events 2 • Up to Day 121
|
6.9%
2/29 • Number of events 2 • Up to Day 121
|
3.6%
1/28 • Number of events 1 • Up to Day 121
|
|
Nervous system disorders
Headache
|
6.1%
2/33 • Number of events 2 • Up to Day 121
|
6.9%
2/29 • Number of events 3 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/33 • Up to Day 121
|
6.9%
2/29 • Number of events 2 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/33 • Up to Day 121
|
6.9%
2/29 • Number of events 2 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
|
Skin and subcutaneous tissue disorders
Haemorrhage Subcutaneous
|
6.1%
2/33 • Number of events 2 • Up to Day 121
|
6.9%
2/29 • Number of events 3 • Up to Day 121
|
3.6%
1/28 • Number of events 1 • Up to Day 121
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/33 • Up to Day 121
|
0.00%
0/29 • Up to Day 121
|
7.1%
2/28 • Number of events 3 • Up to Day 121
|
|
Vascular disorders
Hypertension
|
3.0%
1/33 • Number of events 1 • Up to Day 121
|
17.2%
5/29 • Number of events 5 • Up to Day 121
|
0.00%
0/28 • Up to Day 121
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Prior approval by the Sponsor is required before the results obtained in the clinical study can be made public by the investigator (sub-investigator) in a publication or at a medical meeting.
- Publication restrictions are in place
Restriction type: OTHER