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The purpose of this study is to determine whether ticagrelor is effective in reducing the number of days of pain, intensity of pain, and reducing the use of analgesics due to sickle cell disease
This is a randomised, double-blind, double-dummy, parallel-group, placebo-controlled, study evaluating 2 doses of ticagrelor in 90 patients aged 18 to 30 years, with sickle cell disease (SCD). Patients will be randomised to double-blind double-dummy treatment period in a 1:1:1 ratio (30 to each treatment group) to receive ticagrelor 10 mg twice daily (bid), or ticagrelor 45 mg bid, or placebo bid to determine the frequency of days with pain using an electronic diary (eDiary) every day. Approximately 180 patients will be enrolled. Patient will be followed for safety assessment during and after 2 weeks of treatment completion.
During the 16 week treatment period, patients will complete a daily eDiary concerning daily pain intensity, pain location, use of analgesics and absence from school or work. At the end of the study patients will be asked to rate the change in their sickle cell pain compared to the start of treatment. Platelet aggregation will be measured and reported as P2Y12 reaction units (PRU) pre-dose and 2 hours post-dose at week 4 and week 5 after treatment start. Pharmacokinetic (PK) parameters will be measured at 2 hours post-dose at week 4, and pre-dose and at 2 hours post-dose at week 5. Biomarkers will be assessed pre-dose at week 4, week 5 and week 8. During the study, patients will be evaluated for adverse events (AEs) including bleeding and vaso-occlusive crisis (VOC).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose A | Experimental |
| |
| Dose B | Experimental |
| |
| Placebo | Placebo Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ticagrelor | Drug | Two arms: 1) 10 mg ticagrelor + 45 mg ticagrelor placebo or 2) 45 mg ticagrelor + 10 mg ticagrelor placebo. Drugs taken orally, twice a day (morning and evening, at least 12 hours apart) from randomization until the end of treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Proportion of Days With Pain Due to Sickle Cell Disease as Measured by an eDiary | To investigate the efficacy of 2 different doses of ticagrelor versus placebo in reducing the number of days with pain due to sickle cell disease. | Baseline through Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Average of the Daily Worst Pain Values Reported Via eDiary | To determine the efficacy of 2 different doses of ticagrelor versus placebo in reducing the intensity of pain due to sickle cell disease. Intensity of pain was recorded on an 11-point scale where 0 represented no pain and 10 represented the worst pain imaginable. | Baseline through Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Patients) | To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD | Baseline through Week 12 |
| Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Events) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Maria Ignacia -Berraondo, MD | Quintiles, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Miami | Florida | 33136 | United States | ||
| Research Site |
The study duration was approximately 18 weeks, consisting of a screening period including a 4-week single-blind placebo treatment for baseline assessments, a 12-week double-blind randomised treatment period, and a 2-week follow-up period. A total of 87 patients were randomized
This study was conducted at 26 centers in 8 countries between 09 July 2015 and 16 November 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | PLACEBO 10MG BID + PLACEBO 45MG BID | |
| FG001 | TICAGRELOR 10MG BID + PLACEBO 45MG BID | Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Placebo | Drug | 10 mg ticagrelor placebo + 45 mg ticagrelor placebo. Drugs taken orally, twice a day (morning and evening at least 12 hours apart) from randomization until the end of treatment |
|
| Change in Proportion of Days With Analgesic Use Measured by an eDiary | To assess the efficacy of 2 different doses of ticagrelor versus placebo in reducing the use of analgesics by patients with sickle cell disease. | Baseline through Week 12 |
To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD |
| Baseline through Week 12 |
| Bethesda |
| Maryland |
| 20817 |
| United States |
| Research Site | Charleston | South Carolina | 29425 | United States |
| Research Site | Alexandria | 21131 | Egypt |
| Research Site | Cairo | 11562 | Egypt |
| Research Site | Cairo | 11566 | Egypt |
| Research Site | Bordeaux | 33076 | France |
| Research Site | Strasbourg | 67091 | France |
| Research Site | Verona | 37134 | Italy |
| Research Site | Kikuyu | 00100 | Kenya |
| Research Site | Kisian | 40100 | Kenya |
| Research Site | Nairobi | 40100 | Kenya |
| Research Site | Beirut | 1107 2020 | Lebanon |
| Research Site | Beirut | 113-6044 | Lebanon |
| Research Site | Adana | 01130 | Turkey (Türkiye) |
| Research Site | Mersin | 33079 | Turkey (Türkiye) |
| Research Site | Van | 65080 | Turkey (Türkiye) |
| Research Site | Harrow | HA1 3UJ | United Kingdom |
| Research Site | London | E1 1BB | United Kingdom |
| Research Site | London | E9 6SR | United Kingdom |
| FG002 | TICAGRELOR 45MG BID + PLACEBO 10MG BID |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | PLACEBO 10MG BID + PLACEBO 45MG BID | |
| BG001 | TICAGRELOR 10MG BID + PLACEBO 45MG BID | Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments. |
| BG002 | TICAGRELOR 45MG BID + PLACEBO 10MG BID | |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Proportion of Days With Pain Due to Sickle Cell Disease as Measured by an eDiary | To investigate the efficacy of 2 different doses of ticagrelor versus placebo in reducing the number of days with pain due to sickle cell disease. | The Efficacy analysis set included all randomized patients with at least 1 eDiary record post dose. Patients were analyzed according to their randomized IP. | Posted | Least Squares Mean | 90% Confidence Interval | Proportion of days with pain | Baseline through Week 12 |
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| Secondary | Average of the Daily Worst Pain Values Reported Via eDiary | To determine the efficacy of 2 different doses of ticagrelor versus placebo in reducing the intensity of pain due to sickle cell disease. Intensity of pain was recorded on an 11-point scale where 0 represented no pain and 10 represented the worst pain imaginable. | The Efficacy analysis set included all randomized patients with at least 1 eDiary record post dose. Patients were analyzed according to their randomized IP. | Posted | Mean | Standard Deviation | Average daily worst pain rating | Baseline through Week 12 |
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| Secondary | Change in Proportion of Days With Analgesic Use Measured by an eDiary | To assess the efficacy of 2 different doses of ticagrelor versus placebo in reducing the use of analgesics by patients with sickle cell disease. | The Efficacy analysis set included all randomized patients with at least 1 eDiary record post dose. Patients were analyzed according to their randomized IP. | Posted | Least Squares Mean | 90% Confidence Interval | Proportion of days with analgesic use | Baseline through Week 12 |
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| Other Pre-specified | Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Patients) | To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD | The Safety analysis set included all patients who received at least 1 single dose of randomised IP, ticagrelor or placebo, and for whom any post-dose data were available. Patients were analysed according to the actual treatment. | Posted | Number | Number of patients | Baseline through Week 12 |
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| Other Pre-specified | Number of Major Bleeding or Clinically Relevant Non-major Bleeding Events (Events) | To assess safety and tolerability of 2 different doses of ticagrelor versus placebo in patients with SCD | The Safety analysis set included all patients who received at least 1 single dose of randomised IP, ticagrelor or placebo, and for whom any post-dose data were available. Patients were analysed according to the actual treatment. | Posted | Number | Number of events | Baseline through Week 12 |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | PLACEBO 10MG BID + PLACEBO 45MG BID | 6 | 30 | 16 | 30 | |||
| EG001 | TICAGRELOR 10MG BID + PLACEBO 45MG BID | Note that 1 patient in the Ticagrelor 10mg BID + Placebo 45mg BID group was excluded from the Safety analysis set because they had no post-dose assessments. | 6 | 26 | 15 | 26 | ||
| EG002 | TICAGRELOR 45MG BID + PLACEBO 10MG BID | 5 | 30 | 20 | 30 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Reticulocytopenia | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
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| Sickle cell anaemia with crisis | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
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| Local swelling | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Hepatic ischaemia | Hepatobiliary disorders | MedDRA 19.0 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Face injury | Injury, poisoning and procedural complications | MedDRA 19.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Acute chest syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Vascular occlusion | Vascular disorders | MedDRA 19.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sickle cell anaemia with crisis | Blood and lymphatic system disorders | MedDRA 19.0 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 19.0 | Systematic Assessment |
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| Pain | General disorders | MedDRA 19.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 19.0 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 19.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 19.0 | Systematic Assessment |
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| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA 19.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 19.0 | Systematic Assessment |
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Public disclosure of trial results by Principle Investigators within two years of trial completion requires Sponsor's prior written consent.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Brilinta Global Clinical Leader | AstraZeneca | +46 31 776 10 00 |
| ID | Term |
|---|---|
| D000755 | Anemia, Sickle Cell |
| ID | Term |
|---|---|
| D000745 | Anemia, Hemolytic, Congenital |
| D000743 | Anemia, Hemolytic |
| D000740 | Anemia |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006453 | Hemoglobinopathies |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| D000077486 | Ticagrelor |
| ID | Term |
|---|---|
| D000241 | Adenosine |
| D011684 | Purine Nucleosides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
|
| Unknown or Not Reported |
|
| Mean Difference (Final Values) |
| 0.0801 |
| Standard Error of the Mean |
| 0.06192 |
| 2-Sided |
| 90 |
| -0.0230 |
| 0.1832 |
| Superiority or Other |
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