Trial Outcomes & Findings for Prasugrel Versus Placebo in Adult Sickle Cell Disease (NCT NCT01167023)
NCT ID: NCT01167023
Last Updated: 2012-05-03
Results Overview
A hemorrhagic event requiring medical intervention. Medical intervention was defined as any medical attention resulting in therapy or further investigation during the 30-day treatment duration.
COMPLETED
PHASE2
62 participants
Baseline through 30 days
2012-05-03
Participant Flow
Participant milestones
| Measure |
7.5 mg Prasugrel
Participants were to receive 7.5 milligrams (mg) of prasugrel orally, once daily if they weighed ≥60 kilograms (kg) and if pharmacodynamic (PD) measures indicated that the 5-mg prasugrel dose did not produce a steady-state PD response equivalent to inhibition of platelet activation (IPA) ≥25%. Because these criteria were not met, no participants received 7.5 mg of prasugrel.
|
Placebo
Participants received placebo orally, once daily for 30 days.
|
5 mg Prasugrel
Participants received 5 mg of prasugrel orally, once daily for 30 days.
|
|---|---|---|---|
|
Overall Study
STARTED
|
0
|
21
|
41
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
0
|
19
|
41
|
|
Overall Study
COMPLETED
|
0
|
18
|
39
|
|
Overall Study
NOT COMPLETED
|
0
|
3
|
2
|
Reasons for withdrawal
| Measure |
7.5 mg Prasugrel
Participants were to receive 7.5 milligrams (mg) of prasugrel orally, once daily if they weighed ≥60 kilograms (kg) and if pharmacodynamic (PD) measures indicated that the 5-mg prasugrel dose did not produce a steady-state PD response equivalent to inhibition of platelet activation (IPA) ≥25%. Because these criteria were not met, no participants received 7.5 mg of prasugrel.
|
Placebo
Participants received placebo orally, once daily for 30 days.
|
5 mg Prasugrel
Participants received 5 mg of prasugrel orally, once daily for 30 days.
|
|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
1
|
|
Overall Study
Screen Failure
|
0
|
1
|
0
|
|
Overall Study
Sponsor Decision
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
Baseline Characteristics
Prasugrel Versus Placebo in Adult Sickle Cell Disease
Baseline characteristics by cohort
| Measure |
Placebo
n=21 Participants
Participants received placebo orally, once daily for 30 days.
|
5 mg Prasugrel
n=41 Participants
Participants received 5 mg of prasugrel orally, once daily for 30 days.
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
31.52 years
STANDARD_DEVIATION 8.20 • n=5 Participants
|
32.88 years
STANDARD_DEVIATION 8.60 • n=7 Participants
|
32.42 years
STANDARD_DEVIATION 8.42 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
21 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
21 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
61 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
3 participants
n=5 Participants
|
8 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
Region of Enrollment
United States
|
18 participants
n=5 Participants
|
33 participants
n=7 Participants
|
51 participants
n=5 Participants
|
|
Sickle-Cell Genotype
Hb S ß+ thalassemia genotype
|
2 participants
n=5 Participants
|
4 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
Sickle-Cell Genotype
Hb S ß0 thalassemia genotype
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Sickle-Cell Genotype
Hb SC genotype
|
5 participants
n=5 Participants
|
10 participants
n=7 Participants
|
15 participants
n=5 Participants
|
|
Sickle-Cell Genotype
Hemoglobin SS (Hb SS) genotype
|
13 participants
n=5 Participants
|
24 participants
n=7 Participants
|
37 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline through 30 daysPopulation: Safety population: All randomized participants who took at least 1 dose of study medication. Participants were analyzed according to the treatment they actually received.
A hemorrhagic event requiring medical intervention. Medical intervention was defined as any medical attention resulting in therapy or further investigation during the 30-day treatment duration.
Outcome measures
| Measure |
Placebo
n=19 Participants
Participants received placebo orally, once daily for 30 days.
|
5 mg Prasugrel
n=41 Participants
Participants received 5 mg of prasugrel orally, once daily for 30 days.
|
|---|---|---|
|
Percentage of Participants With Hemorrhagic Events Requiring Medical Intervention During the Treatment Duration
|
0 percentage of participants
|
0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline through 30 daysPopulation: Safety population: All randomized participants who took at least 1 dose of study medication. Participants were analyzed according to the treatment they actually received.
TEAEs were defined as AEs that occurred or worsened after receiving the study drug.
Outcome measures
| Measure |
Placebo
n=19 Participants
Participants received placebo orally, once daily for 30 days.
|
5 mg Prasugrel
n=41 Participants
Participants received 5 mg of prasugrel orally, once daily for 30 days.
|
|---|---|---|
|
Percentage of Participants With Hemorrhagic Treatment-Emergent Adverse Events (TEAEs) During the Treatment Duration
|
5.3 percentage of participants
|
19.5 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline through 30 daysPopulation: Intent to treat (ITT) population consisted of all randomized participants. Participants were analyzed according to the treatment they were randomized to. The analysis was performed in the ITT population who recorded pain intensity in at least 1 daily pain diary.
Participants recorded the intensity of pain due to SCD each day in the daily pain diaries. A scale of 0 to 9 was used, with 0 indicating no pain, and 9 indicating unbearable pain. A response range of 1 to 9 indicated the participant experienced pain due to SCD, whereas a response of 0 indicated participant did not experience pain due to SCD. The percentage of days with pain (pain rate) was calculated as follows: Pain rate = 100\*(Total number of days with pain/number of daily pain diaries completed). Number of daily pain diaries completed was number of nonmissing pain intensity responses.
Outcome measures
| Measure |
Placebo
n=18 Participants
Participants received placebo orally, once daily for 30 days.
|
5 mg Prasugrel
n=40 Participants
Participants received 5 mg of prasugrel orally, once daily for 30 days.
|
|---|---|---|
|
Percentage of Days With Pain Related to Sickle Cell Disease (SCD) During the Treatment Duration
|
63.57 percentage of days
Standard Deviation 41.80
|
39.04 percentage of days
Standard Deviation 42.20
|
SECONDARY outcome
Timeframe: Baseline through 30 daysPopulation: Intent to treat (ITT) population consisted of all randomized participants. Participants were analyzed according to the treatment they were randomized to. The analysis was performed in the ITT population who completed at least 1 page of the daily pain diary or with pain endpoint case report form (CRF) data available.
Pain requiring medical attention was defined 2 ways: (1) if the participant attended an unplanned doctor's appointment or clinic visit, visited the emergency room, or was admitted to hospital due to sickle cell pain, or (2) if the participant experienced a vaso-occlusive crisis (VOC), acute chest syndrome, or hepatic sequestration at least once during the treatment period.
Outcome measures
| Measure |
Placebo
n=19 Participants
Participants received placebo orally, once daily for 30 days.
|
5 mg Prasugrel
n=40 Participants
Participants received 5 mg of prasugrel orally, once daily for 30 days.
|
|---|---|---|
|
Percentage of Participants With Pain Events Related to Sickle Cell Disease (SCD) Requiring Medical Attention During the Treatment Duration
|
36.8 percentage of participants
|
22.5 percentage of participants
|
SECONDARY outcome
Timeframe: 30 daysPopulation: All randomized participants who took at least 1 dose of study medication. Participants were analyzed according to the treatment they actually received. The analysis was performed in the safety population who had both baseline and 30-day PRI measurements and a non-missing genotype.
PRI was calculated by VASP phosphorylation assay using flow cytometry. The PRI indicates the level of P2Y12 inhibition. A low PRI reflects strong inhibition of P2Y12, whereas a high PRI reflects weak/absent inhibition of P2Y12. The Least Squares (LS) Mean values were calculated from a mixed-effects model repeated measures (MMRM) analysis with baseline measurement, stratification variable sickle cell genotype, treatment, time, and time\*treatment interaction as fixed effects, and participant as a random effect in the model.
Outcome measures
| Measure |
Placebo
n=14 Participants
Participants received placebo orally, once daily for 30 days.
|
5 mg Prasugrel
n=30 Participants
Participants received 5 mg of prasugrel orally, once daily for 30 days.
|
|---|---|---|
|
Platelet Reactivity Index (PRI) Measured by Vasodilator-Associated Stimulated Phosphoprotein (VASP) at 30 Days
|
74.843 percentage of PRI
Standard Error 4.993
|
50.792 percentage of PRI
Standard Error 3.360
|
SECONDARY outcome
Timeframe: Baseline through 30 daysPopulation: Intent to treat (ITT) population consisted of all randomized participants. Participants were analyzed according to the treatment they were randomized to. The analysis was performed in the ITT population who had recorded the pain intensity in at least 1 daily pain diary.
Participants recorded intensity of pain due to SCD each day in daily pain diaries using a pain scale. A scale of 0 to 9 was used, with 0=no pain and 9=unbearable pain. A response range of 1 to 9 indicated participant experienced pain due to SCD, whereas a response of 0 indicated participant did not experience pain due to SCD. Pain intensity was the average of a participant's pain ratings. Average pain intensity=(Sum of all nonmissing pain intensity responses/number of daily pain diaries completed). Number of daily pain diaries completed is number of nonmissing pain intensity responses.
Outcome measures
| Measure |
Placebo
n=18 Participants
Participants received placebo orally, once daily for 30 days.
|
5 mg Prasugrel
n=40 Participants
Participants received 5 mg of prasugrel orally, once daily for 30 days.
|
|---|---|---|
|
Intensity of Pain Related to Sickle Cell Disease (SCD) During the Treatment Duration
|
2.72 units on a scale
Standard Deviation 2.33
|
1.56 units on a scale
Standard Deviation 1.98
|
SECONDARY outcome
Timeframe: 30 daysPopulation: Safety population: All randomized participants who took at least 1 dose of study medication. Participants were analyzed according to the treatment they actually received. The analysis was performed in the safety population who had both baseline and 30-day PRU measurements and a non-missing genotype.
PRU represents the rate and extent of adenosine (ADP)-stimulated platelet aggregation. The VN P2Y12 assay is a point-of-care device that measures platelet aggregation with single-use, disposable cartridges. A low PRU reflects stronger inhibition of P2Y12, whereas a high PRU reflects weaker inhibition of P2Y12. The Least Squares Mean values were calculated from a mixed-effects model repeated measures analysis with baseline measurement, stratification variable sickle cell genotype, treatment, time, and time\*treatment interaction as fixed effects, and participant as a random effect in the model.
Outcome measures
| Measure |
Placebo
n=18 Participants
Participants received placebo orally, once daily for 30 days.
|
5 mg Prasugrel
n=35 Participants
Participants received 5 mg of prasugrel orally, once daily for 30 days.
|
|---|---|---|
|
P2Y12 Reaction Units (PRU) as Measured by Accumetrics VerifyNow® P2Y12 (VN P2Y12) at 30 Days
|
336.8 P2Y12 Reaction Units (PRU)
Standard Error 16.8
|
208.5 P2Y12 Reaction Units (PRU)
Standard Error 11.9
|
Adverse Events
Placebo
5 mg Prasugrel
Serious adverse events
| Measure |
Placebo
n=19 participants at risk
Participants received placebo orally, once daily for 30 days.
|
5 mg Prasugrel
n=41 participants at risk
Participants received 5 mg of prasugrel orally, once daily for 30 days.
|
|---|---|---|
|
General disorders
pain
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Blood and lymphatic system disorders
pancytopenia
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Congenital, familial and genetic disorders
sickle cell anaemia
|
0.00%
0/19
|
2.4%
1/41 • Number of events 1
|
|
Congenital, familial and genetic disorders
sickle cell anaemia with crisis
|
5.3%
1/19 • Number of events 1
|
4.9%
2/41 • Number of events 2
|
|
Ear and labyrinth disorders
vertigo
|
0.00%
0/19
|
2.4%
1/41 • Number of events 1
|
|
Infections and infestations
pneumonia
|
0.00%
0/19
|
2.4%
1/41 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
osteonecrosis
|
0.00%
0/19
|
2.4%
1/41 • Number of events 1
|
|
Vascular disorders
thrombosis
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Vascular disorders
vascular occlusion
|
10.5%
2/19 • Number of events 2
|
4.9%
2/41 • Number of events 2
|
Other adverse events
| Measure |
Placebo
n=19 participants at risk
Participants received placebo orally, once daily for 30 days.
|
5 mg Prasugrel
n=41 participants at risk
Participants received 5 mg of prasugrel orally, once daily for 30 days.
|
|---|---|---|
|
General disorders
fatigue
|
10.5%
2/19 • Number of events 2
|
2.4%
1/41 • Number of events 1
|
|
General disorders
malaise
|
5.3%
1/19 • Number of events 2
|
2.4%
1/41 • Number of events 2
|
|
General disorders
pain
|
36.8%
7/19 • Number of events 7
|
26.8%
11/41 • Number of events 21
|
|
Blood and lymphatic system disorders
anaemia
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Congenital, familial and genetic disorders
sickle cell anaemia with crisis
|
0.00%
0/19
|
7.3%
3/41 • Number of events 5
|
|
Eye disorders
ocular icterus
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Eye disorders
photophobia
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Eye disorders
visual impairment
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Gastrointestinal disorders
diarrhoea
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Gastrointestinal disorders
gingival bleeding
|
5.3%
1/19 • Number of events 1
|
4.9%
2/41 • Number of events 4
|
|
Gastrointestinal disorders
haematochezia
|
5.3%
1/19 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
haemorrhoids
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Gastrointestinal disorders
nausea
|
5.3%
1/19 • Number of events 1
|
4.9%
2/41 • Number of events 2
|
|
Gastrointestinal disorders
vomiting
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Hepatobiliary disorders
jaundice
|
5.3%
1/19 • Number of events 1
|
4.9%
2/41 • Number of events 2
|
|
Immune system disorders
drug hypersensitivity
|
5.3%
1/19 • Number of events 3
|
0.00%
0/41
|
|
Immune system disorders
seasonal allergy
|
5.3%
1/19 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Infections and infestations
nasopharyngitis
|
5.3%
1/19 • Number of events 1
|
4.9%
2/41 • Number of events 2
|
|
Infections and infestations
pharyngitis
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Infections and infestations
pharyngitis streptococcal
|
5.3%
1/19 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Injury, poisoning and procedural complications
chorioretinal scar
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Injury, poisoning and procedural complications
sciatic nerve injury
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Investigations
cardiac murmur
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Metabolism and nutrition disorders
decreased appetite
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Metabolism and nutrition disorders
dehydration
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
muscle spasms
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Musculoskeletal and connective tissue disorders
pain in extremity
|
5.3%
1/19 • Number of events 1
|
2.4%
1/41 • Number of events 1
|
|
Nervous system disorders
dizziness
|
5.3%
1/19 • Number of events 1
|
4.9%
2/41 • Number of events 2
|
|
Nervous system disorders
headache
|
15.8%
3/19 • Number of events 3
|
12.2%
5/41 • Number of events 12
|
|
Reproductive system and breast disorders
priapism
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Respiratory, thoracic and mediastinal disorders
dyspnoea exertional
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Vascular disorders
hot flush
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Vascular disorders
thrombosis
|
5.3%
1/19 • Number of events 1
|
0.00%
0/41
|
|
Vascular disorders
vascular occlusion
|
21.1%
4/19 • Number of events 7
|
4.9%
2/41 • Number of events 2
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60