Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2015-001318-92 | EudraCT Number |
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The study was stopped due to operational feasibility and not due to any safety concerns
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The purpose of this study is to compare the efficacy and safety of 2 starting doses of ponatinib compared to nilotinib in participants with imatinib-resistant chronic myeloid leukemia (CML) in chronic phase (CP).
This is a multi-center, randomized study to demonstrate the efficacy and safety of 2 starting doses of ponatinib as a treatment for CP-CML compared to nilotinib. Eligible participants must have chronic phase chronic myeloid leukemia (CP-CML), be resistant to first-line imatinib treatment and have received no other tyrosine kinase inhibitors (TKIs).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort A: Ponatinib 30 mg | Experimental | Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to 42 months. |
|
| Cohort B: Ponatinib 15 mg | Experimental | Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to 45 months. |
|
| Cohort C: Nilotinib 400 mg | Active Comparator | Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ponatinib 30 mg QD | Drug | Ponatinib 30 mg, taken orally once daily. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Major Molecular Response (MMR) | MMR is defined as the percentage of participants achieving a ratio of ≤0.1% Breakpoint Cluster Region-Abelson (BCR ABL) to ABL transcripts on the international scale (≤0.1% BCR-ABL/ABL[IS]) at any time within 12 months after randomization. | Up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Major Cytogenetic Response (MCyR) | MCyR was the percentage of participants achieving Complete cytogenetic response (CCyR: defined as 0% Philadelphia chromosome-positive [Ph+] metaphases by cytogenetic analysis of bone marrow) or Partial Cytogenetic Response (PCyR: defined as >0% to 35% Ph+ metaphases by cytogenetic analysis of bone marrow) at any time within 12 months after randomization. |
Not provided
Inclusion Criteria:
Have CP-CML and are resistant to first-line imatinib treatment.
Be male or female ≥18 years old.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Have adequate renal function as defined by the following criterion:
• Serum creatinine ≤1.5 × upper limit of normal (ULN) for institution.
Have adequate hepatic function as defined by all of the following criteria:
Have normal pancreatic status as defined by the following criterion:
Exclusion Criteria:
Have previously been treated with any approved or investigational TKIs other than imatinib or treated with imatinib within 14 days prior to receiving study drug.
Have previously been treated with any anti-CML therapy other than hydroxyurea, including interferon, cytarabine, immunotherapy, or any cytotoxic chemotherapy, radiotherapy, or investigational therapy.
Underwent autologous or allogeneic stem cell transplant.
Are in CCyR or MMR.
Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cliniques Universitaire Saint-Luc (Site 058) | Brussels | 1200 | Belgium |
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Participants with a diagnosis of chronic phase-chronic myeloid leukemia were enrolled and randomised at a ratio of 1:2:1 to receive ponatinib 30 mg and ponatinib 15 mg compared with nilotinib 400 mg.
Participants took part in the study at 90 investigative sites in Austria, Canada, Czechia, France, Hungary, Italy, Korea, and Russia from 31 December 2015 to 20 January 2021
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort A: Ponatinib 30 mg | Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months. |
| FG001 | Cohort B: Ponatinib 15 mg | Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months. |
| FG002 | Cohort C: Nilotinib 400 mg | Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Safety Population included all participants who have received at least 1 dose of study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort A: Ponatinib 30 mg | Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months. |
| BG001 | Cohort B: Ponatinib 15 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Percentage of Participants With Major Molecular Response (MMR) | MMR is defined as the percentage of participants achieving a ratio of ≤0.1% Breakpoint Cluster Region-Abelson (BCR ABL) to ABL transcripts on the international scale (≤0.1% BCR-ABL/ABL[IS]) at any time within 12 months after randomization. | Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 12 months |
|
All-cause mortality: From first dose up to end of study (Up to approximately 60 months); for serious and other adverse events: from first dose up to 30 days post last dose (Up to approximately 46 months)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort A: Ponatinib 30 mg | Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA23.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA23.0 | Systematic Assessment |
This study was terminated due to operational feasibility and not due to any safety concerns.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Takeda | +1-877-825-3327 | TrialDisclosures@takeda.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 10, 2017 | Oct 28, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 31, 2016 | Oct 28, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D015466 | Leukemia, Myeloid, Chronic-Phase |
| D007938 | Leukemia |
| D007951 | Leukemia, Myeloid |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| ID | Term |
|---|---|
| D006425 | Hemic and Lymphatic Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| C545373 | ponatinib |
| C498826 | nilotinib |
| C494814 | BID protein, human |
Not provided
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| Ponatinib 15 mg QD | Drug | Ponatinib 15 mg, taken orally once daily. |
|
|
| Nilotinib 400 mg BID | Drug | Nilotinib 400 mg, taken orally twice daily. |
|
|
| Up to 12 months |
| Percentage of Participants With Complete Cytogenetic Response (CCyR) | CCyR rate was defined as the percentage of participants achieving CCyR up to 12 months after randomization. CCyR is defined as 0% Philadelphia chromosome-positive [Ph+] metaphases by cytogenetic analysis of bone marrow. | Up to 12 months |
| Percentage of Participants With Molecular Response (MR) | Molecular response rate is defined as percentage of participants achieving MR2: Molecular response with 2-log reduction (defined as ≤1% BCR-ABL[IS]), MMR: Major molecular responder, MR4 (defined as ≤0.01% BCR-ABL[IS]), and MR4.5 (defined as ≤0.0032% BCR-ABL[IS]) after randomization. | From Month 3 to every 3 months up to 48 months |
| Percentage of Participants With MR1 | MR1 was defined as the percentage of participants achieving a ratio of ≤10% BCR ABL to ABL transcripts on the international scale at 3 months. | Month 3 |
| Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | TE-AOE: arterial occlusive event with an initial onset date on or after first dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on or after first dose date. TE-VTE: vascular occlusive event with an initial onset date on or after first dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on or after first dose date. AE: any untoward medical occurrence in participant administered pharmaceutical product; untoward medical occurrence does not necessarily have causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is congenital anomaly/birth defect/is medically important event. | From first dose up to 30 days post last dose (Up to approximately 46 months) |
| Time to Response | Time to MMR defined as the interval between the randomization date and the first date at which the criteria for response was met. MMR was defined as <=0.1% BCR-ABL. | Up to approximately 60 months |
| Duration of Response | Duration of response defined as the interval between the first assessment at which the criteria for response was met until the earliest date at which loss of response occurs, or the criteria for progression was met. | Up to approximately 60 months |
| Progression-free Survival (PFS) | Progression-free survival (PFS) defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression was met (progression to AP- or BP CML), or death due to any cause, censored at the last response assessment. | Up to end of study (approximately 60 months) |
| Overall Survival | Overall survival (OS) defined as the interval between the first dose date of study treatment and date of death due to any cause, censored at the last contact date to be alive. | Up to end of study (approximately 60 months) |
| Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR) | CHR rate is defined as the percentage of participants achieving CHR at any time after initiation of study treatment. CHR is defined as achieving all of the following measurements: White blood cells (WBC) ≤ institutional upper limit of normal (ULN); Platelets <450 x 10^9/L; No blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; Basophils in peripheral blood <5%; No extramedullary involvement (including no hepatomegaly or splenomegaly). | 3 months after the first dose of study treatment |
| Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. | From first dose up to end of treatment (Up to approximately 45 months) |
| Percentage of Participants With Progression to Accelerated Phase (AP) or Blast Phase (BP)-CML | Progression to AP is defined as: >=15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*10^9 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP-CML is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly. | Up to end of study (Up to approximately 60 months) |
| Lack of Efficacy |
|
| Lost to Follow-up |
|
| Pregnancy |
|
| Study Terminated by Sponsor |
|
| Physician Decision |
|
| Withdrawal by Subject |
|
| Reason not Specified |
|
| Randomized but not Treated |
|
Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months. |
| BG002 | Cohort C: Nilotinib 400 mg | Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Height | Number analyzed is the number of participants with data available for Height at Baseline. | Mean | Standard Deviation | cm |
|
| Weight | Mean | Standard Deviation | kg |
|
| Body Mass Index (BMI) | BMI is calculated as weight (kg) divided by square of height (m^2). | Number analyzed is the number of participants with data available for BMI at Baseline. | Mean | Standard Deviation | kg/m^2 |
|
| OG001 |
| Cohort B: Ponatinib 15 mg |
Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months. |
| OG002 | Cohort C: Nilotinib 400 mg | Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months. |
|
|
| Secondary | Percentage of Participants With Major Cytogenetic Response (MCyR) | MCyR was the percentage of participants achieving Complete cytogenetic response (CCyR: defined as 0% Philadelphia chromosome-positive [Ph+] metaphases by cytogenetic analysis of bone marrow) or Partial Cytogenetic Response (PCyR: defined as >0% to 35% Ph+ metaphases by cytogenetic analysis of bone marrow) at any time within 12 months after randomization. | Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 12 months |
|
|
|
| Secondary | Percentage of Participants With Complete Cytogenetic Response (CCyR) | CCyR rate was defined as the percentage of participants achieving CCyR up to 12 months after randomization. CCyR is defined as 0% Philadelphia chromosome-positive [Ph+] metaphases by cytogenetic analysis of bone marrow. | Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 12 months |
|
|
|
| Secondary | Percentage of Participants With Molecular Response (MR) | Molecular response rate is defined as percentage of participants achieving MR2: Molecular response with 2-log reduction (defined as ≤1% BCR-ABL[IS]), MMR: Major molecular responder, MR4 (defined as ≤0.01% BCR-ABL[IS]), and MR4.5 (defined as ≤0.0032% BCR-ABL[IS]) after randomization. | Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis. Number analyzed are participants with data available for analyses at given timepoint. | Posted | Number | percentage of participants | From Month 3 to every 3 months up to 48 months |
|
|
|
| Secondary | Percentage of Participants With MR1 | MR1 was defined as the percentage of participants achieving a ratio of ≤10% BCR ABL to ABL transcripts on the international scale at 3 months. | Safety Population includes all participants who have received at least 1 dose of study drug, with data available for analysis. | Posted | Number | percentage of participants | Month 3 |
|
|
|
| Secondary | Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs) | TE-AOE: arterial occlusive event with an initial onset date on or after first dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on or after first dose date. TE-VTE: vascular occlusive event with an initial onset date on or after first dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on or after first dose date. AE: any untoward medical occurrence in participant administered pharmaceutical product; untoward medical occurrence does not necessarily have causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is congenital anomaly/birth defect/is medically important event. | Safety Population includes all participants who have received at least 1 dose of study drug. | Posted | Number | percentage of participants | From first dose up to 30 days post last dose (Up to approximately 46 months) |
|
|
|
| Secondary | Time to Response | Time to MMR defined as the interval between the randomization date and the first date at which the criteria for response was met. MMR was defined as <=0.1% BCR-ABL. | Safety Population includes all participants who have received at least 1 dose of study drug. Only responders were analyzed for this outcome measure. | Posted | Median | 95% Confidence Interval | months | Up to approximately 60 months |
|
|
|
| Secondary | Duration of Response | Duration of response defined as the interval between the first assessment at which the criteria for response was met until the earliest date at which loss of response occurs, or the criteria for progression was met. | Safety Population includes all participants who have received at least 1 dose of study drug. Only responders were analyzed for this outcome measure. | Posted | Median | 95% Confidence Interval | months | Up to approximately 60 months |
|
|
|
| Secondary | Progression-free Survival (PFS) | Progression-free survival (PFS) defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression was met (progression to AP- or BP CML), or death due to any cause, censored at the last response assessment. | Safety Population includes all participants who have received at least 1 dose of study drug. | Posted | Median | 95% Confidence Interval | months | Up to end of study (approximately 60 months) |
|
|
|
| Secondary | Overall Survival | Overall survival (OS) defined as the interval between the first dose date of study treatment and date of death due to any cause, censored at the last contact date to be alive. | Safety Population includes all participants who have received at least 1 dose of study drug. | Posted | Median | 95% Confidence Interval | months | Up to end of study (approximately 60 months) |
|
|
|
| Secondary | Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR) | CHR rate is defined as the percentage of participants achieving CHR at any time after initiation of study treatment. CHR is defined as achieving all of the following measurements: White blood cells (WBC) ≤ institutional upper limit of normal (ULN); Platelets <450 x 10^9/L; No blasts or promyelocytes in peripheral blood; <5% myelocytes plus metamyelocytes in peripheral blood; Basophils in peripheral blood <5%; No extramedullary involvement (including no hepatomegaly or splenomegaly). | Safety Population includes all participants who have received at least 1 dose of study drug. | Posted | Number | 95% Confidence Interval | percentage of participants | 3 months after the first dose of study treatment |
|
|
|
| Secondary | Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption | An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. | Safety Population includes all participants who have received at least 1 dose of study drug. | Posted | Number | percentage of participants | From first dose up to end of treatment (Up to approximately 45 months) |
|
|
|
| Secondary | Percentage of Participants With Progression to Accelerated Phase (AP) or Blast Phase (BP)-CML | Progression to AP is defined as: >=15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*10^9 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP-CML is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly. | As the study was terminated, data was not collected and analyzed for this outcome measure. | Posted | Up to end of study (Up to approximately 60 months) |
|
|
| 1 |
| 10 |
| 4 |
| 10 |
| 10 |
| 10 |
| EG001 | Cohort B: Ponatinib 15 mg | Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months. | 1 | 21 | 3 | 21 | 20 | 21 |
| EG002 | Cohort C: Nilotinib 400 mg | Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months. | 0 | 12 | 2 | 12 | 12 | 12 |
| Sepsis | Infections and infestations | MedDRA23.0 | Systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA23.0 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA23.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA23.0 | Systematic Assessment |
|
| Atrial flutter | Cardiac disorders | MedDRA23.0 | Systematic Assessment |
|
| Pancreatitis acute | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA23.0 | Systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA23.0 | Systematic Assessment |
|
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Peripheral arterial occlusive disease | Vascular disorders | MedDRA23.0 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA23.0 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA23.0 | Systematic Assessment |
|
| Anaemia folate deficiency | Blood and lymphatic system disorders | MedDRA23.0 | Systematic Assessment |
|
| Splenic lesion | Blood and lymphatic system disorders | MedDRA23.0 | Systematic Assessment |
|
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA23.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Blood cholesterol increased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Platelet count increased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Blood magnesium decreased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Blood phosphorus decreased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Blood triglycerides increased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| N-terminal prohormone brain natriuretic peptide increased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA23.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA23.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA23.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA23.0 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA23.0 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA23.0 | Systematic Assessment |
|
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA23.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Dental caries | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Inguinal hernia | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Hypertriglyceridaemia | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Hyperglycaemia | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Diabetes mellitus | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Hyperlipidaemia | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Hypophosphataemia | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Hypophosphataemia | Gastrointestinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA23.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA23.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA23.0 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA23.0 | Systematic Assessment |
|
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA23.0 | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | MedDRA23.0 | Systematic Assessment |
|
| Hepatitis viral | Infections and infestations | MedDRA23.0 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA23.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA23.0 | Systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA23.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA23.0 | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA23.0 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA23.0 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA23.0 | Systematic Assessment |
|
| Paternal exposure timing unspecified | Injury, poisoning and procedural complications | MedDRA23.0 | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA23.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA23.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA23.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA23.0 | Systematic Assessment |
|
| Essential hypertension | Vascular disorders | MedDRA23.0 | Systematic Assessment |
|
| Peripheral artery stenosis | Vascular disorders | MedDRA23.0 | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA23.0 | Systematic Assessment |
|
| Left ventricular hypertrophy | Cardiac disorders | MedDRA23.0 | Systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | MedDRA23.0 | Systematic Assessment |
|
| Sinus arrhythmia | Cardiac disorders | MedDRA23.0 | Systematic Assessment |
|
| Arrhythmia supraventricular | Cardiac disorders | MedDRA23.0 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA23.0 | Systematic Assessment |
|
| Dilatation atrial | Cardiac disorders | MedDRA23.0 | Systematic Assessment |
|
| Right atrial hypertrophy | Cardiac disorders | MedDRA23.0 | Systematic Assessment |
|
| Right ventricular dilatation | Cardiac disorders | MedDRA23.0 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | MedDRA23.0 | Systematic Assessment |
|
| Tricuspid valve incompetence | Cardiac disorders | MedDRA23.0 | Systematic Assessment |
|
| Retinal vascular disorder | Eye disorders | MedDRA23.0 | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA23.0 | Systematic Assessment |
|
| Periorbital oedema | Eye disorders | MedDRA23.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA23.0 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA23.0 | Systematic Assessment |
|
| Asthenia | General disorders | MedDRA23.0 | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA23.0 | Systematic Assessment |
|
| Bronchial obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Pulmonary artery dilatation | Respiratory, thoracic and mediastinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA23.0 | Systematic Assessment |
|
| Hepatitis toxic | Hepatobiliary disorders | MedDRA23.0 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA23.0 | Systematic Assessment |
|
| Ocular icterus | Hepatobiliary disorders | MedDRA23.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA23.0 | Systematic Assessment |
|
The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
| D013568 |
| Pathological Conditions, Signs and Symptoms |
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| MR2 - Month 6 |
|
|
| MR2 - Month 9 |
|
|
| MR2 - Month 12 |
|
|
| MR2 - Month 15 |
|
|
| MR2 - Month 18 |
|
|
| MR2 - Month 21 |
|
|
| MR2 - Month 24 |
|
|
| MR2 - Month 27 |
|
|
| MR2 - Month 30 |
|
|
| MR2 - Month 33 |
|
|
| MR2 - Month 36 |
|
|
| MR2 - Month 39 |
|
|
| MR2 - Month 42 |
|
|
| MR2 - Month 45 |
|
|
| MR2 - Month 48 |
|
|
| MR3/MMR - Month 3 |
|
|
| MR3/MMR - Month 6 |
|
|
| MR3/MMR - Month 9 |
|
|
| MR3/MMR - Month 12 |
|
|
| MR3/MMR - Month 15 |
|
|
| MR3/MMR - Month 18 |
|
|
| MR3/MMR - Month 21 |
|
|
| MR3/MMR - Month 24 |
|
|
| MR3/MMR - Month 27 |
|
|
| MR3/MMR - Month 30 |
|
|
| MR3/MMR - Month 33 |
|
|
| MR3/MMR - Month 36 |
|
|
| MR3/MMR - Month 39 |
|
|
| MR3/MMR - Month 42 |
|
|
| MR3/MMR - Month 45 |
|
|
| MR3/MMR - Month 48 |
|
|
| MR4 - Month 3 |
|
|
| MR4 - Month 6 |
|
|
| MR4 - Month 9 |
|
|
| MR4 - Month 12 |
|
|
| MR4 - Month 15 |
|
|
| MR4 - Month 18 |
|
|
| MR4 - Month 21 |
|
|
| MR4 - Month 24 |
|
|
| MR4 - Month 27 |
|
|
| MR4 - Month 30 |
|
|
| MR4 - Month 33 |
|
|
| MR4 - Month 36 |
|
|
| MR4 - Month 39 |
|
|
| MR4 - Month 42 |
|
|
| MR4 - Month 45 |
|
|
| MR4 - Month 48 |
|
|
| MR4.5 - Month 3 |
|
|
| MR4.5 - Month 6 |
|
|
| MR4.5 - Month 9 |
|
|
| MR4.5 - Month 12 |
|
|
| MR4.5 - Month 15 |
|
|
| MR4.5 - Month 18 |
|
|
| MR4.5 - Month 21 |
|
|
| MR4.5 - Month 24 |
|
|
| MR4.5 - Month 27 |
|
|
| MR4.5 - Month 30 |
|
|
| MR4.5 - Month 33 |
|
|
| MR4.5 - Month 36 |
|
|
| MR4.5 - Month 39 |
|
|
| MR4.5 - Month 42 |
|
|
| MR4.5 - Month 45 |
|
|
| MR4.5 - Month 48 |
|
|
| Title | Measurements |
|---|---|
|
| AEs |
|
| SAEs |
|
|
| TEAEs Leading to Dose Interruption |
|