Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2014-005199-27 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
This is a multicenter, randomized, double-blind study being conducted as a postmarketing requirement to the US Food and Drug Administration (FDA) to evaluate whether there is a lower starting dosage of lenvatinib 24 mg once daily (QD) that provides comparable efficacy but has a better safety profile in participants with radioiodine-refractory differentiated thyroid cancer RR-DTC with radiographic evidence of disease progression within the prior 12 months.
This study consists of 2 phases, the Prerandomization Phase and the Randomization Phase. The Prerandomization Phase will last no longer than 28 days and will include a Screening Period to establish protocol eligibility and a Baseline Period to confirm eligibility and establish disease characteristics prior to randomization and treatment.
The Randomization Phase will consist of a Treatment Period and a Follow-up Period. It will begin at the time of randomization of the first participant and will consist of 28-day blinded study treatment cycles. The data cutoff for the primary analysis will occur at the end of the Randomization Phase, which is defined as when the last participant enrolled completes the Week 24 tumor assessments or discontinues study treatment if before Week 24.
Participants on treatment at the time of data cutoff for the primary analysis will remain on blinded investigational product until the primary analysis has been completed, after which they will transition to commercial lenvatinib outside the study. The last participant's last assessment (Off-treatment visit) will be the End of Study.
Participants will be randomly assigned to treatment with 1 of 2 blinded starting dosages of lenvatinib in a 1:1 ratio to receive lenvatinib 18 mg or 24 mg orally once daily (QD). Dose reductions will occur in succession based on the previous dose level (24, 20, 14, 10, and 8 mg QD, or 18, 14, 10, 8, and 4 mg QD, respectively). Once the dose has been reduced, it may not be increased at a later date.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 24 mg Lenvatinib | Experimental | Participants will receive 24 mg once daily (QD) as the starting dose. Dose reductions will occur in succession based on the previous dose level (24, 20, 14, 10, or 8 mg QD). To maintain blinded treatment assignment, participants will be administered study drug in the form of two 10-mg capsules and two 4-mg capsules containing either lenvatinib or placebo (total of 4 capsules) to be taken orally, at approximately the same time each morning and may be taken in a fasting state or following a meal. |
|
| 18 mg Lenvatinib | Experimental | Participants will receive 18mg QD as the starting dose. Dose reductions will occur in succession based on the previous dose level (18,14, 10, 8, or 4 mg QD). To maintain blinded treatment assignment, participants will be administered study drug in the form of two 10-mg capsules and two 4-mg capsules containing either lenvatinib or placebo (total of 4 capsules) to be taken orally, at approximately the same time each morning and may be taken in a fasting state or following a meal. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lenvatinib | Drug | Lenvatinib capsule. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate (ORR) as of Week 24 (ORR24wk) | ORR as of Week 24 was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) as of the Week 24 time point or earlier, as measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD. | From the date of randomization up to Week 24 |
| Percentage of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs) in the First 24 Weeks | This outcome measure reports TEAEs in the first 24 weeks only. A TEAE was defined as any adverse event (AE) that had an onset date on or after the first dose of study drug up to 28 days following the last dose of study drug, or a worsening in severity from Baseline (pretreatment). In addition, if an AE reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, it was also counted as a TEAE. A severity grade was defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. As per CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE. | Baseline up to Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) | PFS, defined as the time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurs first, as measured by RECIST V1.1. PD: 20% increase in the sum of the pertinent diameters (SOD) of target lesions, taking as reference the smallest sum SOD recorded since the treatment started or the appearance of one or more new lesions. PFS was analyzed using the Kaplan-Meier method. As planned, data for this endpoint was analyzed and collected till Primary completion date. |
Not provided
Inclusion Criteria:
Participants must have histologically or cytologically confirmed diagnosis of one of the following differentiated thyroid cancer (DTC) subtypes:
Papillary thyroid cancer (PTC)
Follicular thyroid cancer (FTC)
Measurable disease meeting the following criteria and confirmed by central radiographic review:
Participants must show evidence of disease progression within 12 months (an additional month will be allowed to accommodate actual dates of performance of screening scans, that is, within less than or equal to <=13 months) prior to signing informed consent, according to RECIST 1.1 assessed and confirmed by central radiographic review of CT and/or MRI scans.
Participants must be Iodine-131 refractory/resistant as defined by at least one of the following:
Participants with known brain metastases who have completed whole brain radiotherapy, stereotactic radiosurgery or complete surgical resection, will be eligible if they have remained clinically stable, asymptomatic, and off steroids for one month.
Participants must be receiving thyroxine suppression therapy and thyroid stimulating hormone (TSH) should not be elevated (TSH should be <=5.50 micro-international units per liter [mcIU/ML]). When tolerated by the participant, thyroxine dose should be changed to achieve TSH suppression (TSH <0.50 mcIU/ML) and this dose may be changed concurrently upon starting study drug treatment.
All chemotherapy or radiation-related toxicities must have resolved to Grade <2 severity per Common Terminology Criteria for Adverse Events (CTCAE v4.03), except alopecia and infertility.
Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at Screening and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1.
Adequate renal function defined as calculated creatinine clearance >=30 mL/min per the Cockcroft and Gault formula.
Adequate bone marrow function:
Adequate blood coagulation function as evidenced by an International Normalized Ratio (INR) <=1.5.
Adequate liver function:
Males or females age >=18 years at the time of informed consent.
Females must not be lactating or pregnant at Screening or Baseline (as documented by a negative beta-human chorionic gonadotropin [B-hCG] test with a minimum sensitivity of 25 IU/L or equivalent units of B-hCG. A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug.
All females will be considered to be of childbearing potential unless they are postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age group and without other known or suspected cause) or have been sterilized surgically (ie, bilateral tubal ligation, total hysterectomy or bilateral oophorectomy, all with surgery at least 1 month before dosing).
Females of childbearing potential should avoid becoming pregnant and use highly effective contraception while on treatment with lenvatinib and for at least 1 month after finishing treatment. Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (example, total abstinence, an intrauterine device, a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation. Women using oral hormonal contraceptives should add a barrier method.
Participants must voluntarily agree to provide written informed consent.
Participants must be willing and able to comply with all aspects of the protocol.
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Facility#1 | La Jolla | California | 92093 | United States | ||
| Facility #1 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36464853 | Derived | Taylor MH, Leboulleux S, Panaseykin Y, Konda B, de La Fouchardiere C, Hughes BGM, Gianoukakis AG, Park YJ, Romanov I, Krzyzanowska MK, Garbinsky D, Sherif B, Pan JJ, Binder TA, Sauter N, Xie R, Brose MS. Health-related quality-of-life analyses from a multicenter, randomized, double-blind phase 2 study of patients with differentiated thyroid cancer treated with lenvatinib 18 or 24 mg/day. Cancer Med. 2023 Feb;12(4):4332-4342. doi: 10.1002/cam4.5308. Epub 2022 Dec 4. | |
| 34664662 |
Not provided
Not provided
A total of 241 participants were screened and enrolled of which 89 participants were screen failures, and 152 participants were randomized and treated.
Participants took part in the study at 38 investigative sites in the North America, Europe, Russia, Australia, and Asia. As planned, the study was unblinded after the primary analysis was completed and all participants were treated with open-label lenvatinib at their current dose level at the discretion of the investigator until they were transitioned to commercially available lenvatinib.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Lenvatinib 24 mg | Participants received lenvatinib 24 mg, capsule, orally, once daily in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first (up to 35 months). To maintain blinded treatment assignment, participants received a total of 4 capsules in the form of two 10-mg capsules and one 4-mg capsule containing lenvatinib and one 4-mg placebo capsule. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
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 | Jan 9, 2020 | Dec 7, 2020 |
Not provided
Not provided
Not provided
Not provided
| Lenvatinib matching placebo | Drug | Lenvatinib matching placebo capsule. |
|
| Time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurs first up to approximately 2 years 6 months |
| PFS After Next Line of Treatment (PFS2) | PFS2, defined as the time from randomization to PD on next-line treatment, or death from any cause, whichever occurred first, as measured by RECIST V1.1. PD: 20% increase in the SOD of target lesions, taking as reference the smallest sum SOD recorded since the treatment started or the appearance of one or more new lesions. PFS was analyzed using the Kaplan-Meier method. As planned, data for this endpoint was analyzed and collected till Primary completion date. | Time from randomization to PD on next-line treatment or death from any cause, whichever occurs first up to approximately 2 years 6 months |
| Number of Participants With TEAE and Serious Adverse Events (SAEs) | TEAEs were defined as those AEs that occurred (or worsened, if present at Baseline) after the first dose of study drug through 28 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. SAE was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. | From date of first administration of study drug up to 28 days after last dose of study drug up to approximately 3 years 3 months |
| Time to Treatment Discontinuation Due to an Adverse Event (AE) | Time to Treatment Discontinuation due to an AE (such as abdominal distention, appendicitis perforated, arthralgia, anemia, etc) was analyzed using the Kaplan-Meier method. As planned, data for this endpoint was analyzed and collected till Primary completion date. | From date of first administration of study drug up to approximately 2 years 6 months |
| Number of Dose Reductions | Number of dose reduction was reported as number of participants who underwent one or more number of dose reductions. As planned, data for this endpoint was analyzed and collected till Primary completion date. | From date of first administration of study drug up to approximately 2 years 6 months |
| Time to First Dose Reduction | Time to First Dose Reduction was analyzed using the Kaplan-Meier method. As planned, data for this endpoint was analyzed and collected till Primary completion date. | From date of first administration of study drug up to approximately 2 years 6 months |
| Model Predicted Apparent Total Clearance (CL/F) Following Oral Dosing of Lenvatinib | Sparse pharmacokinetic (PK) samples (approximately 9 per participant) were collected and analyzed using a population PK approach to estimate PK parameters. Lenvatinib total plasma concentration data were pooled with data from studies E7080-G000-303 (NCT01321554) and E7080-G000-201 (NCT00784303), and a population PK model was applied to the pooled dataset. Individual predicted CL/F for lenvatinib was then derived from the PK model by starting dose. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| Model Predicted Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib | Sparse PK samples (approximately 9 per participant) were collected and analyzed using a population PK approach to estimate PK parameters. Lenvatinib total plasma concentration data were pooled with data from studies E7080-G000-303 (NCT01321554) and E7080-G000-201 (NCT00784303), and a population PK model was applied to the pooled dataset. Individual predicted AUC for lenvatinib was then derived from the PK model by starting dose. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| Parameter Estimates From the Population Pharmacokinetic/Pharmacodynamic (PK/PD) Model Describing the Relationship Between Lenvatinib Exposure (AUC) and Thyroglobulin Levels | The relationship between exposure to lenvatinib and change from baseline in thyroglobulin was planned to be analyzed using a model-based approach. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| Parameter Estimates From the Population Pharmacokinetic/Pharmacodynamic (PK/PD) Model Describing the Relationship Between Lenvatinib Exposure (AUC) and Thyroid-Stimulating Hormone (TSH) Levels | The relationship between exposure to lenvatinib and change from baseline in TSH was planned to be analyzed using a model-based approach. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| Baseline Level Estimates From the Population PK/PD Model Describing the Relationship Between Lenvatinib Exposure (AUC) and Vascular Endothelial Growth Factor (VEGF), Soluble Tie-2, Angiopoietin-2 (Ang-2) and Fibroblast Growth Factor-23 (FGF23) Levels | Per the planned population PK/PD analysis for this endpoint, Arms/Groups were combined and lenvatinib total plasma concentration and serum biomarker data for VEGF, Ang-2, soluble Tie-2, and FGF23 from this study were combined with data from study E7080-G000-303 (NCT01321554). The relationship between lenvatinib exposure at the time of measurement of biomarker was described using PK/PD modelling. Initially, PK/PD models were developed individually for each biomarker and then combined into a single combined model. Changes in biomarker levels over time related to lenvatinib exposure were best described by an indirect response, sigmoidal Emax model. For the final combined model, baseline level estimates were determined separately for each biomarker. The data presented are the model predicted baseline estimates, with Measure Type "Number." They are population PK/PD model predictions and have been estimated using non-linear mixed effects modelling. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| Mean Residence Time (MRT) Estimates From the Population PK/PD Model Describing the Relationship Between Lenvatinib Exposure (AUC) and VEGF, Soluble Tie-2, Ang-2 and FGF23 Levels | Per the planned population PK/PD analysis for this endpoint, Arms/Groups were combined and lenvatinib total plasma concentration and serum biomarker data for VEGF, Ang-2, soluble Tie-2, and FGF23 from this study were combined with data from study E7080-G000-303 (NCT01321554). The relationship between lenvatinib exposure at the time of measurement of biomarker was described using PK/PD modelling. Initially, PK/PD models were developed individually for each biomarker and then combined into a single combined model. Changes in biomarker levels over time related to lenvatinib exposure were best described by an indirect response, sigmoidal Emax model. For the final combined model, MRT estimates were determined separately for each biomarker. The data presented are the model predicted MRT estimates, with Measure Type "Number." They are population PK/PD model predictions and have been estimated using non-linear mixed effects modelling. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| Hill Coefficient Estimates From the Population PK/PD Model Describing the Relationship Between Lenvatinib Exposure (AUC) and VEGF, Soluble Tie-2, Ang-2 and FGF23 Levels | Per the planned population PK/PD analysis for this endpoint, Arms/Groups were combined and lenvatinib total plasma concentration and serum biomarker data for VEGF, Ang-2, soluble Tie-2, and FGF23 from this study were combined with data from study E7080-G000-303 (NCT01321554). The relationship between lenvatinib exposure at the time of measurement of biomarker was described using PK/PD modelling. Initially, PK/PD models were developed individually for each biomarker and then combined into a single combined model. Changes in biomarker levels over time related to lenvatinib exposure were best described by an indirect response, sigmoidal Emax model. For the final combined model, Hill Coefficient estimates were determined separately for each biomarker. The data presented are the model predicted Hill Coefficient estimates, with Measure Type "Number." They are population PK/PD model predictions and (&) have been estimated using non-linear mixed effects modelling. | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| Parameter Estimates From the PK/PD Model for Tumor Growth Inhibition and Serum Biomarkers Tie-2 and Ang-2 | Per the planned analysis, Arms/Groups were combined & tumor-growth inhibition models based on lenvatinib & placebo data from this study combined with study NCT01321554. Effects of tumor growth rate, drug effects, tumor resistance, & tumor size reduction related to biomarker response were assessed. Longitudinal data of sum of the longest diameter for target lesion by investigator assessment in this study & independent reviewer assessment in study NCT01321554 were used. Changes in Ang-2 & soluble Tie-2 were evaluated, individually & in combination for their impact on tumor size. The concomitant use of lenvatinib & biomarker changes due to drug effects as predictors of tumor size were also evaluated. The final integrated model for tumor growth & biomarkers included effects of lenvatinib exposure & tumor growth reduction related to Tie-2 & Ang-2 biomarkers as significant predictors. Data presented are the parameters defining this non-linear mixed effects model, with Measure Type "Number." | Baseline up to week 120 |
| Lenvatinib Mean AUC Resulting in 50% of the Emax (EC50) Estimate From the PK/PD Model for Tumor Growth Inhibition and Serum Biomarkers Tie-2 and Ang-2 | Per the planned analysis, Arms/Groups were combined & tumor-growth inhibition models based on lenvatinib & placebo data from this study combined with study NCT01321554. Effects of tumor growth rate, drug effects, tumor resistance, & tumor size reduction related to biomarker response were assessed. Longitudinal data of the sum of the longest diameter for target lesion by investigator assessment in this study & independent reviewer assessment in study NCT01321554 were used. Changes in Ang-2 & soluble Tie-2 were evaluated, individually & in combination for their impact on tumor size. The concomitant use of lenvatinib & biomarker changes due to drug effects as predictors of tumor size were also evaluated. The final integrated model for tumor growth & biomarkers included effects of lenvatinib exposure & tumor growth reduction related to Tie-2 & Ang-2 biomarkers as significant predictors. Data presented are EC50 estimated using non-linear mixed effects modeling, with Measure Type "Number." | Baseline up to week 120 |
| Scale Factor Estimate for Final Parametric Time to Event PK/PD Model for PFS | Per planned analysis, Arms/Groups were combined & PK/PD analysis for PFS was based on lenvatinib & placebo data from this study combined with NCT01321554. Relationship between lenvatinib exposure & PFS was assessed using Kaplan-Meier plots. A parametric survival model (proportional hazard model) with Weibull distribution structure was developed to estimate the probability distribution of time from study start to progression, as a function of covariates including baseline disease characteristics, demographics, lenvatinib exposure, changes in biomarker time profiles, model predicted change from baseline in tumor size & change in tumor size time-profiles. Significant (p<0.01) covariates from the univariate analysis were added to the model simultaneously & significant predictors were retained according to backward exclusion criteria (log likelihood ratio test, p-value of 0.001). Data presented are scale factor estimated using non-linear mixed effects modeling, with Measure Type "Number." | Time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 3 years 3 months |
| Shape Factor Estimate for Final Parametric Time to Event PK/PD Model for PFS | Per planned analysis, Arms/Groups were combined & PK/PD analysis for PFS was based on lenvatinib & placebo data from this study combined with NCT01321554. Relationship between lenvatinib exposure & PFS was assessed using Kaplan-Meier plots. A parametric survival model (proportional hazard model) with Weibull distribution structure was developed to estimate the probability distribution of time from study start to progression, as a function of covariates including baseline disease characteristics, demographics, lenvatinib exposure, changes in biomarker time profiles, model predicted change from baseline in tumor size & change in tumor size time-profiles. Significant (p<0.01) covariates from the univariate analysis were added to the model simultaneously & significant predictors were retained according to backward exclusion criteria (log likelihood ratio test, p-value of 0.001). Data presented are shape factor estimated using non-linear mixed effects modeling, with Measure Type "Number." | Time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 3 years 3 months |
| Lenvatinib AUC Exposure Effect Estimate for Final Parametric Time to Event PK/PD Model for PFS | Per planned analysis, Arms/Groups were combined & PK/PD analysis for PFS was based on lenvatinib & placebo data from this study combined with NCT01321554. Relationship between lenvatinib exposure & PFS was assessed using Kaplan-Meier plots. A parametric survival model (proportional hazard model) with Weibull distribution structure was developed to estimate probability distribution of time from study start to progression, as a function of covariates including baseline disease characteristics, demographics, lenvatinib exposure, changes in biomarker time profiles, model predicted change from baseline in tumor size & change in tumor size time-profiles. Significant (p<0.01) covariates from the univariate analysis were added to the model simultaneously & significant predictors retained according to backward exclusion criteria (log likelihood ratio test, p-value of 0.001). Data presented are AUC exposure effect estimated using non-linear mixed effects modeling, with Measure Type "Number." | Time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 3 years 3 months |
| Predicted Percent Change in Tumor Size Estimate for Final Parametric Time to Event PK/PD Model for PFS | Per planned analysis, Arms/Groups were combined & PK/PD analysis for PFS based on lenvatinib & placebo data from this study combined with NCT01321554. Relationship between lenvatinib exposure & PFS was assessed using Kaplan-Meier plots. A parametric survival model (proportional hazard model) with Weibull distribution structure was developed to estimate probability distribution of time from study start to progression, as a function of covariates including baseline disease characteristics, demographics, lenvatinib exposure, changes in biomarker time profiles, model predicted change from baseline tumor size & change in tumor size time-profiles. Significant (p<0.01) covariates from univariate analysis were added to the model simultaneously & significant predictors retained according to backward exclusion criteria (log likelihood ratio test, p-value = 0.001). Data presented are the predicted change in tumor size estimated using non-linear mixed effects modeling, with Measure Type "Number." | Time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 3 years 3 months |
| Baseline Tumor Size Estimate for Final Parametric Time to Event PK/PD Model for PFS | Per planned analysis Arms/Groups were combined & PK/PD analysis for PFS was based on lenvatinib & placebo data from this study combined with E7080-G000-303(NCT01321554).Relationship between lenvatinib exposure & PFS was assessed using Kaplan-Meier plots.Parametric survival model(proportional hazard model)with Weibull distribution structure was developed to estimate probability distribution of time from study start to progression as function of covariates including baseline disease characteristics,demographics,lenvatinib exposure,changes in biomarker time profiles,model predicted change from baseline tumor size & change in tumor size time-profiles.Significant(p<0.01)covariates from univariate analysis were added to model simultaneously & significant predictors retained as per backward exclusion criteria(log likelihood ratio test,p-value of 0.001).Data presented are predicted baseline tumor size from the model with Measure Type "Number"estimated using non-linear mixed effects modelling. | Time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 3 years 3 months |
| Input Rate Indirect Effect Model Estimate From Base/Final PK/PD Blood Pressure Model | Per the planned analysis, Arms/Groups were combined and population PK/PD analysis for blood pressure was based on lenvatinib and placebo pooled data from this study combined with study E7080-G000-201 (NCT00784303) & study E7080-G000-303 (NCT01321554). The effect of lenvatinib exposure (AUC) at the time of blood pressure assessment on systolic and diastolic blood pressure was tested as a simultaneous indirect model where lenvatinib AUC was linked to the input rate of the indirect effect model by a linear slope factor function. Based on the results from model development, an indirect PK/PD model with a linear effect of lenvatinib exposure on both systolic and diastolic blood pressure was selected as the base model for subsequent univariate analysis. The data presented are the input rate indirect effect model estimate, with Measure Type "Number." They are population PK/PD model predictions and have been estimated using mixed effects non-linear modeling. | From date of first administration of study drug up to 6 months |
| Drug Effect on Systolic and Diastolic Input Rate Estimates From Base/Final PK/PD Blood Pressure Model | Per the planned analysis, Arms/Groups were combined and population PK/PD analysis for blood pressure was based on lenvatinib and placebo pooled data from this study combined with study E7080-G000-201 (NCT00784303) & study E7080-G000-303 (NCT01321554). The effect of lenvatinib exposure (AUC) at the time of blood pressure assessment on systolic and diastolic blood pressure was tested as a simultaneous indirect model where lenvatinib AUC was linked to the input rate of the indirect effect model by a linear slope factor function. Based on the results from model development, an indirect PK/PD model with a linear effect of lenvatinib exposure on both systolic and diastolic blood pressure was selected as the base model for subsequent univariate analysis. The data presented are the input rate indirect effect model estimate, with Measure Type "Number." They are population PK/PD model predictions and have been estimated using non-linear mixed effects modeling. | From date of first administration of study drug up to 6 months |
| Number of Participants With Weight Decrease Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined and a population PK/PD analysis of the relationship between lenvatinib exposure and occurrence of the TEAE weight decreased was based on placebo and lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) and study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE weight decreased and lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, and random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE and a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate) or Grade 3 (severe or medically significant) TEAE were estimated as a function of lenvatinib or exposure. | Up to 3 years 3 months |
| Number of Participants With Hypertension Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined & a population PK/PD analysis of the relationship between lenvatinib exposure & occurrence of the TEAE hypertension was based on placebo & lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) & study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE hypertension & lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, & random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE & a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe or medically significant) or Grade 4 (life-threatening consequences) TEAE were estimated as a function of lenvatinib or exposure. | Up to 3 years 3 months |
| Number of Participants With Proteinuria Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined and a population PK/PD analysis of the relationship between lenvatinib exposure and occurrence of the TEAE proteinuria was based on placebo and lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) and study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE proteinuria and lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, and random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE and a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate), or Grade 3 (severe or medically significant) TEAE were estimated as a function of lenvatinib or exposure. | Up to 3 years 3 months |
| Number of Participants With Fatigue Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined and a population PK/PD analysis of the relationship between lenvatinib exposure and occurrence of the TEAE fatigue was based on placebo and lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) and study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE fatigue and lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, and random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE and a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate) or Grade 3 (severe or medically significant) TEAE were estimated as a function of lenvatinib or exposure. | Up to 3 years 3 months |
| Number of Participants With Diarrhea Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined and a population PK/PD analysis of the relationship between lenvatinib exposure and occurrence of the TEAE diarrhea was based on placebo and lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) and study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE diarrhea and lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, and random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE and a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate) or Grade 3 (severe or medically significant) TEAE were estimated as a function of lenvatinib or exposure. | Up to 3 years 3 months |
| Number of Participants With Nausea Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined and a population PK/PD analysis of the relationship between lenvatinib exposure and occurrence of the TEAE nausea was based on placebo and lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) and study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE nausea and lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, and random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE and a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate) or Grade 3 (severe or medically significant) TEAE were estimated as a function of lenvatinib or exposure. | Up to 3 years 3 months |
| Number of Participants With Vomiting Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined and a population PK/PD analysis of the relationship between lenvatinib exposure and occurrence of the TEAE vomiting was based on placebo and lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) and study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE vomiting and lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, and random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE and a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate) or Grade 3 (severe or medically significant) TEAE were estimated as a function of lenvatinib or exposure. | Up to 3 years 3 months |
| Change From Baseline in the Health-Related Quality of Life (HRQoL) Assessed by European Quality of Life (EuroQol) Five-Dimensional, 3-Level (EQ-5D-3L) Index Score and Visual Analogue Scale (VAS) | The EQ-5D-3L is a health profile questionnaire assessing quality of life along 5 dimensions. Participants rate 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 5-15 with "5" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. EQ-5D-3L also included an EQ visual analogue scale (VAS) that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Decrease from baseline in EQ-5D-3L signifies improvement. Total index EQ-5D-3L summary score was weighted with a range of -0.594 (worst) to 1.0 (best). EQ-5D-3L also included an EQ health utilities index (HUI) where 1 indicated full health while a score of 0 indicated worst health/death. | Baseline, Week 8, 16, and 24 |
| Change From Baseline in the HRQoL Assessed by Functional Assessment of Cancer Therapy-General (FACT-G) Total Score | The FACT-G is a 27-item questionnaire that measures the effect of cancer treatment on quality of life that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being). Each item has a 5-point scale response set (0: not at all; 1: a little bit; 2: somewhat; 3: quite a bit; and 4: very much). The FACT-G total score ranges between 0 and 108. Higher score indicates better quality of life. | Baseline, Week 8, 16 and 24 |
| San Diego |
| California |
| 92307 |
| United States |
| Facility #1 | Torrance | California | 90502 | United States |
| Facility #1 | Washington D.C. | District of Columbia | 20010 | United States |
| Facility #1 | Boston | Massachusetts | 02114 | United States |
| Facility #2 | Boston | Massachusetts | 02115 | United States |
| Facility #1 | Ann Arbor | Michigan | 48109 | United States |
| Facility #1 | Detroit | Michigan | 48201 | United States |
| Facility#2 | Morristown | New Jersey | 07962 | United States |
| Facility#1 | Summit | New Jersey | 07902 | United States |
| Facility #1 | The Bronx | New York | 10461 | United States |
| Facility #1 | Columbus | Ohio | 43210 | United States |
| Facility #1 | Portland | Oregon | 97239 | United States |
| Facility #2 | Philadelphia | Pennsylvania | 19104 | United States |
| Facility #1 | Philadelphia | Pennsylvania | 19111 | United States |
| Facility #1 | Seattle | Washington | 98109 | United States |
| Facility #1 | Darlinghurst | New South Wales | Australia |
| Facility #1 | Saint Leonards | New South Wales | Australia |
| Royal Brisbane and Women's Hospital | Brisbane | Queensland | 4006 | Australia |
| Facility#2 | Chermside | Queensland | Australia |
| Facility #1 | Herston | Queensland | Australia |
| Facility #1 | Melbourne | Victoria | Australia |
| Facility #1 | Nedlands | Western Australia | Australia |
| Facility #1 | Melbourne | Australia |
| Facility #1 | Saint Leonards | Australia |
| Facility #1 | Edegem | Antwerpen | 2650 | Belgium |
| Facility #1 | Brussels | Brussels Capital | 1200 | Belgium |
| Facility #2 | Namur | 5000 | Belgium |
| Facility #1 | Namur | Belgium |
| Facility #1 | Calgary | Alberta | Canada |
| Facility #1 | Toronto | Ontario | Canada |
| Facility #1 | Québec | Canada |
| Facility #1 | Odense | Region Syddanmark | DK-5000 | Denmark |
| Facility #1 | Strasbourg | Bas-Rhin | France |
| Facility #1 | Caen | Calvados | 14076 | France |
| Facility #1 | Dijon | Cote-d'Or | 21079 | France |
| Facility #1 | Bordeaux | Gironde | France |
| Facility #1 | Angers | Maine-et-Loire | France |
| Facility #2 | Villejuif | Val-de-Marne | 94805 | France |
| Facility #1 | Villejuif | Val-de-Marne | France |
| Facility #2 | Angers | 49933 | France |
| Facility #1 | Bordeaux | 33076 | France |
| Facility #1 | Caen | France |
| Facility #1 | Dijon | 21079 | France |
| Facility #2 | Lyon | 69373 | France |
| Facility #1 | Paris | 75013 | France |
| Facility #1 | Tübingen | Baden-Wurttemberg | 72076 | Germany |
| Facility #1 | Würzburg | Bavaria | 97080 | Germany |
| Facility #1 | Hanover | Lower Saxony | 30625 | Germany |
| Facility #1 | Essen | North Rhine-Westphalia | Germany |
| Facility #2 | Essen | North Rhine-Westphalia | Germany |
| Facility #1 | Essen | 45147 | Germany |
| Facility #1 | Leipzig | Germany |
| Facility #1 | Petah Tikva | Israel |
| Facility #6 | Rome | Lazio | 144 | Italy |
| Facility #1 | Rome | Lazio | Italy |
| Facility #2 | Rome | Lazio | Italy |
| Facility #3 | Rome | Lazio | Italy |
| Facility #2 | Milan | Lombardy | Italy |
| Facility #3 | Milan | Lombardy | Italy |
| Facility #4 | Milan | Lombardy | Italy |
| Facility #5 | Milan | Lombardy | Italy |
| Facility #1 | Livorno | Tuscany | 57100 | Italy |
| Facility #1 | Pisa | Tuscany | Italy |
| Facility #6 | Milan | 20122 | Italy |
| Facility #7 | Milan | 20149 | Italy |
| Facility #2 | Pisa | 56124 | Italy |
| Facility #4 | Roma | Italy |
| Facility #2 | Rozzano | Italy |
| Facility #1 | Torino | Italy |
| Facility #1 | Viagrande | Italy |
| Facility #2 | Kielce | Poland |
| Facility #1 | Cluj-Napoca | Cluj | 400058 | Romania |
| Facility #1 | Bucharest | 11863 | Romania |
| Facility #4 | Saint Petersburg | Leningradskaya O | 197758 | Russia |
| Facility #3 | Moscow | 115478 | Russia |
| Facility #4 | Moscow | 117036 | Russia |
| Facility #1 | Moscow | Russia |
| Facility #2 | Moscow | Russia |
| Facility #1 | Obninsk | 249036 | Russia |
| Facility #3 | Saint Petersburg | 197758 | Russia |
| Facility #1 | Saint Petersburg | Russia |
| Facility #2 | Saint Petersburg | Russia |
| Facility#1 | Busan | 49241 | South Korea |
| Facility #1 | Goyang-si | South Korea |
| Facility #3 | Seoul | 135-710 | South Korea |
| Facility #4 | Seoul | 137-701 | South Korea |
| Facility #1 | Seoul | South Korea |
| Facility #2 | Seoul | South Korea |
| Facility #1 | Barcelona | Catalonia | Spain |
| Facility #2 | Madrid | Madrid, Communidad Delaware | Spain |
| Facility #1 | Badalona | 8035 | Spain |
| Facility #2 | Barcelona | 8036 | Spain |
| Facility #1 | Madrid | 28034 | Spain |
| Facility #2 | Madrid | Spain |
| Facility #3 | Madrid | Spain |
| Facility #1 | Málaga | 29010 | Spain |
| Facility #1 | Gothenburg | SE-41345 | Sweden |
| Facility #1 | Lund | SE-22185 | Sweden |
| Facility #1 | London | City of London | United Kingdom |
| Facility #1 | Glasgow | Glasgow City | United Kingdom |
| Derived |
| Brose MS, Panaseykin Y, Konda B, de la Fouchardiere C, Hughes BGM, Gianoukakis AG, Joo Park Y, Romanov I, Krzyzanowska MK, Leboulleux S, Binder TA, Dutcus C, Xie R, Taylor MH. A Randomized Study of Lenvatinib 18 mg vs 24 mg in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer. J Clin Endocrinol Metab. 2022 Feb 17;107(3):776-787. doi: 10.1210/clinem/dgab731. |
| FG001 | Lenvatinib 18 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first (up to 35 months). To maintain blinded treatment assignment, participants received a total of 4 capsules in the form of one 10-mg capsule and two 4-mg capsules containing lenvatinib and one 10-mg placebo capsule. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Full analysis set (FAS) included all participants randomly assigned to treatment.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Lenvatinib 24 mg | Participants received lenvatinib 24 mg, capsule, orally, once daily in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first (up to 35 months). To maintain blinded treatment assignment, participants received a total of 4 capsules in the form of two 10-mg capsules and one 4-mg capsule containing lenvatinib and one 4-mg placebo capsule. |
| BG001 | Lenvatinib 18 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first (up to 35 months). To maintain blinded treatment assignment, participants received a total of 4 capsules in the form of one 10-mg capsule and two 4-mg capsules containing lenvatinib and one 10-mg placebo capsule. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| 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 |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| 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 | Objective Response Rate (ORR) as of Week 24 (ORR24wk) | ORR as of Week 24 was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR) as of the Week 24 time point or earlier, as measured by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). CR: was disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in short axis to less than (<) 10 millimeter (mm). PR: was at least a 30 percent (%) decrease in sum of diameter (SOD) of target lesions, taking as reference the baseline SOD. | FAS included all participants randomly assigned to treatment. | Posted | Number | 95% Confidence Interval | percentage of participants | From the date of randomization up to Week 24 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Percentage of Participants With Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs) in the First 24 Weeks | This outcome measure reports TEAEs in the first 24 weeks only. A TEAE was defined as any adverse event (AE) that had an onset date on or after the first dose of study drug up to 28 days following the last dose of study drug, or a worsening in severity from Baseline (pretreatment). In addition, if an AE reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, it was also counted as a TEAE. A severity grade was defined by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03. As per CTCAE, Grade 1 scales as Mild; Grade 2 scales as Moderate; Grade 3 scales as severe or medically significant but not immediately life threatening; Grade 4 scales as life-threatening consequences; and Grade 5 scales as death related to AE. | Safety analysis set included all participants randomly assigned to treatment and who received at least 1 dose of study drug. | Posted | Number | percentage of participants | Baseline up to Week 24 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Progression-free Survival (PFS) | PFS, defined as the time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurs first, as measured by RECIST V1.1. PD: 20% increase in the sum of the pertinent diameters (SOD) of target lesions, taking as reference the smallest sum SOD recorded since the treatment started or the appearance of one or more new lesions. PFS was analyzed using the Kaplan-Meier method. As planned, data for this endpoint was analyzed and collected till Primary completion date. | FAS included all participants randomly assigned to treatment. | Posted | Median | 95% Confidence Interval | months | Time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurs first up to approximately 2 years 6 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | PFS After Next Line of Treatment (PFS2) | PFS2, defined as the time from randomization to PD on next-line treatment, or death from any cause, whichever occurred first, as measured by RECIST V1.1. PD: 20% increase in the SOD of target lesions, taking as reference the smallest sum SOD recorded since the treatment started or the appearance of one or more new lesions. PFS was analyzed using the Kaplan-Meier method. As planned, data for this endpoint was analyzed and collected till Primary completion date. | FAS included all participants randomly assigned to treatment. | Posted | Median | 95% Confidence Interval | months | Time from randomization to PD on next-line treatment or death from any cause, whichever occurs first up to approximately 2 years 6 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With TEAE and Serious Adverse Events (SAEs) | TEAEs were defined as those AEs that occurred (or worsened, if present at Baseline) after the first dose of study drug through 28 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a participants or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. SAE was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. | Safety analysis set included all participants randomly assigned to treatment and who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | From date of first administration of study drug up to 28 days after last dose of study drug up to approximately 3 years 3 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to Treatment Discontinuation Due to an Adverse Event (AE) | Time to Treatment Discontinuation due to an AE (such as abdominal distention, appendicitis perforated, arthralgia, anemia, etc) was analyzed using the Kaplan-Meier method. As planned, data for this endpoint was analyzed and collected till Primary completion date. | Safety analysis set included all participants randomly assigned to treatment and who received at least 1 dose of study drug. | Posted | Median | 95% Confidence Interval | weeks | From date of first administration of study drug up to approximately 2 years 6 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Dose Reductions | Number of dose reduction was reported as number of participants who underwent one or more number of dose reductions. As planned, data for this endpoint was analyzed and collected till Primary completion date. | Safety analysis set included all participants randomly assigned to treatment and who received at least 1 dose of study drug. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Count of Participants | Participants | From date of first administration of study drug up to approximately 2 years 6 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to First Dose Reduction | Time to First Dose Reduction was analyzed using the Kaplan-Meier method. As planned, data for this endpoint was analyzed and collected till Primary completion date. | Safety analysis set included all participants randomly assigned to treatment and who received at least 1 dose of study drug. | Posted | Median | 95% Confidence Interval | weeks | From date of first administration of study drug up to approximately 2 years 6 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Model Predicted Apparent Total Clearance (CL/F) Following Oral Dosing of Lenvatinib | Sparse pharmacokinetic (PK) samples (approximately 9 per participant) were collected and analyzed using a population PK approach to estimate PK parameters. Lenvatinib total plasma concentration data were pooled with data from studies E7080-G000-303 (NCT01321554) and E7080-G000-201 (NCT00784303), and a population PK model was applied to the pooled dataset. Individual predicted CL/F for lenvatinib was then derived from the PK model by starting dose. | PK Analysis Set included all participants who received at least one dose of study drug and who had evaluable lenvatinib plasma concentration data. Population for Lenvatinib 24 mg arm for this outcome measure included participants from study E7080-G000-303 (NCT01321554), E7080-G000-201 (NCT00784303) and from this current study E7080-G000-211. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | liter per hour (L/h) | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Model Predicted Area Under the Plasma Drug Concentration-time Curve (AUC) for Lenvatinib | Sparse PK samples (approximately 9 per participant) were collected and analyzed using a population PK approach to estimate PK parameters. Lenvatinib total plasma concentration data were pooled with data from studies E7080-G000-303 (NCT01321554) and E7080-G000-201 (NCT00784303), and a population PK model was applied to the pooled dataset. Individual predicted AUC for lenvatinib was then derived from the PK model by starting dose. | PK Analysis Set included all participants who received at least one dose of study drug and who had evaluable lenvatinib plasma concentration data. Population for Lenvatinib 24 mg arm for this outcome measure included participants from study E7080-G000-303 (NCT01321554), E7080-G000-201 (NCT00784303) and from this current study E7080-G000-211. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | nanogram*hour per milliliter (ng*h/mL) | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Parameter Estimates From the Population Pharmacokinetic/Pharmacodynamic (PK/PD) Model Describing the Relationship Between Lenvatinib Exposure (AUC) and Thyroglobulin Levels | The relationship between exposure to lenvatinib and change from baseline in thyroglobulin was planned to be analyzed using a model-based approach. | PK/PD modeling of the effect of lenvatinib exposure on thyroglobulin levels could not be achieved due to the high variability in change from baseline data and hence data was not collected and reported. | Posted | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Parameter Estimates From the Population Pharmacokinetic/Pharmacodynamic (PK/PD) Model Describing the Relationship Between Lenvatinib Exposure (AUC) and Thyroid-Stimulating Hormone (TSH) Levels | The relationship between exposure to lenvatinib and change from baseline in TSH was planned to be analyzed using a model-based approach. | PK/PD modeling of the effect of lenvatinib exposure on TSH levels could not be achieved due to the high variability in change from baseline data and hence data was not collected and reported. | Posted | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Baseline Level Estimates From the Population PK/PD Model Describing the Relationship Between Lenvatinib Exposure (AUC) and Vascular Endothelial Growth Factor (VEGF), Soluble Tie-2, Angiopoietin-2 (Ang-2) and Fibroblast Growth Factor-23 (FGF23) Levels | Per the planned population PK/PD analysis for this endpoint, Arms/Groups were combined and lenvatinib total plasma concentration and serum biomarker data for VEGF, Ang-2, soluble Tie-2, and FGF23 from this study were combined with data from study E7080-G000-303 (NCT01321554). The relationship between lenvatinib exposure at the time of measurement of biomarker was described using PK/PD modelling. Initially, PK/PD models were developed individually for each biomarker and then combined into a single combined model. Changes in biomarker levels over time related to lenvatinib exposure were best described by an indirect response, sigmoidal Emax model. For the final combined model, baseline level estimates were determined separately for each biomarker. The data presented are the model predicted baseline estimates, with Measure Type "Number." They are population PK/PD model predictions and have been estimated using non-linear mixed effects modelling. | PK/PD analysis was performed for differentiated thyroid cancer (DTC) participants who received lenvatinib or placebo in study E7080-G000-303 (NCT01321554) and current study E7080-G000-211 and provided both PK data for lenvatinib and baseline and post-dose serum biomarkers samples. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies participants who were evaluable for given categories. | Posted | Number | 95% Confidence Interval | nanogram per liter (ng/L) | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Mean Residence Time (MRT) Estimates From the Population PK/PD Model Describing the Relationship Between Lenvatinib Exposure (AUC) and VEGF, Soluble Tie-2, Ang-2 and FGF23 Levels | Per the planned population PK/PD analysis for this endpoint, Arms/Groups were combined and lenvatinib total plasma concentration and serum biomarker data for VEGF, Ang-2, soluble Tie-2, and FGF23 from this study were combined with data from study E7080-G000-303 (NCT01321554). The relationship between lenvatinib exposure at the time of measurement of biomarker was described using PK/PD modelling. Initially, PK/PD models were developed individually for each biomarker and then combined into a single combined model. Changes in biomarker levels over time related to lenvatinib exposure were best described by an indirect response, sigmoidal Emax model. For the final combined model, MRT estimates were determined separately for each biomarker. The data presented are the model predicted MRT estimates, with Measure Type "Number." They are population PK/PD model predictions and have been estimated using non-linear mixed effects modelling. | PK/PD analysis was performed for DTC participants who received lenvatinib or placebo in study E7080-G000-303 (NCT01321554) and current study E7080-G000-211 and provided both PK data for lenvatinib and baseline and post-dose serum biomarkers samples. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies participants who were evaluable for given categories. | Posted | Number | 95% Confidence Interval | hours | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Hill Coefficient Estimates From the Population PK/PD Model Describing the Relationship Between Lenvatinib Exposure (AUC) and VEGF, Soluble Tie-2, Ang-2 and FGF23 Levels | Per the planned population PK/PD analysis for this endpoint, Arms/Groups were combined and lenvatinib total plasma concentration and serum biomarker data for VEGF, Ang-2, soluble Tie-2, and FGF23 from this study were combined with data from study E7080-G000-303 (NCT01321554). The relationship between lenvatinib exposure at the time of measurement of biomarker was described using PK/PD modelling. Initially, PK/PD models were developed individually for each biomarker and then combined into a single combined model. Changes in biomarker levels over time related to lenvatinib exposure were best described by an indirect response, sigmoidal Emax model. For the final combined model, Hill Coefficient estimates were determined separately for each biomarker. The data presented are the model predicted Hill Coefficient estimates, with Measure Type "Number." They are population PK/PD model predictions and (&) have been estimated using non-linear mixed effects modelling. | PK/PD analysis was performed for DTC participants who received lenvatinib or placebo in study E7080-G000-303 (NCT01321554) and current study E7080-G000-211 and provided both PK data for lenvatinib and baseline and post-dose serum biomarkers samples. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies participants who were evaluable for given categories. | Posted | Number | 95% Confidence Interval | unitless | Cycle 1 Day 1: 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 8: predose, Cycle 1 Day 15: predose, 0.5-4 hours and 6-10 hours postdose; Cycle 1 Day 22: optionally at predose; Cycle 2 Day 1: predose and 2-12 hours postdose (Cycle length=28 days) |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Parameter Estimates From the PK/PD Model for Tumor Growth Inhibition and Serum Biomarkers Tie-2 and Ang-2 | Per the planned analysis, Arms/Groups were combined & tumor-growth inhibition models based on lenvatinib & placebo data from this study combined with study NCT01321554. Effects of tumor growth rate, drug effects, tumor resistance, & tumor size reduction related to biomarker response were assessed. Longitudinal data of sum of the longest diameter for target lesion by investigator assessment in this study & independent reviewer assessment in study NCT01321554 were used. Changes in Ang-2 & soluble Tie-2 were evaluated, individually & in combination for their impact on tumor size. The concomitant use of lenvatinib & biomarker changes due to drug effects as predictors of tumor size were also evaluated. The final integrated model for tumor growth & biomarkers included effects of lenvatinib exposure & tumor growth reduction related to Tie-2 & Ang-2 biomarkers as significant predictors. Data presented are the parameters defining this non-linear mixed effects model, with Measure Type "Number." | PK/PD analysis was performed for DTC participants who received lenvatinib or placebo in study E7080-G000-303 (NCT01321554) and this current study E7080-G000-211 who had PK data and at least one post-baseline tumor evaluation. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | per week | Baseline up to week 120 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Lenvatinib Mean AUC Resulting in 50% of the Emax (EC50) Estimate From the PK/PD Model for Tumor Growth Inhibition and Serum Biomarkers Tie-2 and Ang-2 | Per the planned analysis, Arms/Groups were combined & tumor-growth inhibition models based on lenvatinib & placebo data from this study combined with study NCT01321554. Effects of tumor growth rate, drug effects, tumor resistance, & tumor size reduction related to biomarker response were assessed. Longitudinal data of the sum of the longest diameter for target lesion by investigator assessment in this study & independent reviewer assessment in study NCT01321554 were used. Changes in Ang-2 & soluble Tie-2 were evaluated, individually & in combination for their impact on tumor size. The concomitant use of lenvatinib & biomarker changes due to drug effects as predictors of tumor size were also evaluated. The final integrated model for tumor growth & biomarkers included effects of lenvatinib exposure & tumor growth reduction related to Tie-2 & Ang-2 biomarkers as significant predictors. Data presented are EC50 estimated using non-linear mixed effects modeling, with Measure Type "Number." | PK/PD analysis was performed for DTC participants who received lenvatinib or placebo in study E7080-G000-303 (NCT01321554) and this current study E7080-G000-211 who had PK data and at least one post-baseline tumor evaluation. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | ng*h/mL | Baseline up to week 120 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Scale Factor Estimate for Final Parametric Time to Event PK/PD Model for PFS | Per planned analysis, Arms/Groups were combined & PK/PD analysis for PFS was based on lenvatinib & placebo data from this study combined with NCT01321554. Relationship between lenvatinib exposure & PFS was assessed using Kaplan-Meier plots. A parametric survival model (proportional hazard model) with Weibull distribution structure was developed to estimate the probability distribution of time from study start to progression, as a function of covariates including baseline disease characteristics, demographics, lenvatinib exposure, changes in biomarker time profiles, model predicted change from baseline in tumor size & change in tumor size time-profiles. Significant (p<0.01) covariates from the univariate analysis were added to the model simultaneously & significant predictors were retained according to backward exclusion criteria (log likelihood ratio test, p-value of 0.001). Data presented are scale factor estimated using non-linear mixed effects modeling, with Measure Type "Number." | PK/PD analysis for PFS was performed for DTC participants who received lenvatinib or placebo in study E7080-G000-303 (NCT01321554) and this current study E7080-G000-211. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | per week | Time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 3 years 3 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Shape Factor Estimate for Final Parametric Time to Event PK/PD Model for PFS | Per planned analysis, Arms/Groups were combined & PK/PD analysis for PFS was based on lenvatinib & placebo data from this study combined with NCT01321554. Relationship between lenvatinib exposure & PFS was assessed using Kaplan-Meier plots. A parametric survival model (proportional hazard model) with Weibull distribution structure was developed to estimate the probability distribution of time from study start to progression, as a function of covariates including baseline disease characteristics, demographics, lenvatinib exposure, changes in biomarker time profiles, model predicted change from baseline in tumor size & change in tumor size time-profiles. Significant (p<0.01) covariates from the univariate analysis were added to the model simultaneously & significant predictors were retained according to backward exclusion criteria (log likelihood ratio test, p-value of 0.001). Data presented are shape factor estimated using non-linear mixed effects modeling, with Measure Type "Number." | PK/PD analysis for PFS was performed for DTC participants who received lenvatinib or placebo in study E7080-G000-303 (NCT01321554) and this current study E7080-G000-211. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | unitless | Time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 3 years 3 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Lenvatinib AUC Exposure Effect Estimate for Final Parametric Time to Event PK/PD Model for PFS | Per planned analysis, Arms/Groups were combined & PK/PD analysis for PFS was based on lenvatinib & placebo data from this study combined with NCT01321554. Relationship between lenvatinib exposure & PFS was assessed using Kaplan-Meier plots. A parametric survival model (proportional hazard model) with Weibull distribution structure was developed to estimate probability distribution of time from study start to progression, as a function of covariates including baseline disease characteristics, demographics, lenvatinib exposure, changes in biomarker time profiles, model predicted change from baseline in tumor size & change in tumor size time-profiles. Significant (p<0.01) covariates from the univariate analysis were added to the model simultaneously & significant predictors retained according to backward exclusion criteria (log likelihood ratio test, p-value of 0.001). Data presented are AUC exposure effect estimated using non-linear mixed effects modeling, with Measure Type "Number." | PK/PD analysis for PFS was performed for DTC participants who received lenvatinib or placebo in study E7080-G000-303 (NCT01321554) and this current study E7080-G000-211. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | per microgram*week per milliliter | Time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 3 years 3 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Predicted Percent Change in Tumor Size Estimate for Final Parametric Time to Event PK/PD Model for PFS | Per planned analysis, Arms/Groups were combined & PK/PD analysis for PFS based on lenvatinib & placebo data from this study combined with NCT01321554. Relationship between lenvatinib exposure & PFS was assessed using Kaplan-Meier plots. A parametric survival model (proportional hazard model) with Weibull distribution structure was developed to estimate probability distribution of time from study start to progression, as a function of covariates including baseline disease characteristics, demographics, lenvatinib exposure, changes in biomarker time profiles, model predicted change from baseline tumor size & change in tumor size time-profiles. Significant (p<0.01) covariates from univariate analysis were added to the model simultaneously & significant predictors retained according to backward exclusion criteria (log likelihood ratio test, p-value = 0.001). Data presented are the predicted change in tumor size estimated using non-linear mixed effects modeling, with Measure Type "Number." | PK/PD analysis for PFS was performed for DTC participants who received lenvatinib or placebo in study E7080-G000-303 (NCT01321554) and this current study E7080-G000-211. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | percent change | Time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 3 years 3 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Baseline Tumor Size Estimate for Final Parametric Time to Event PK/PD Model for PFS | Per planned analysis Arms/Groups were combined & PK/PD analysis for PFS was based on lenvatinib & placebo data from this study combined with E7080-G000-303(NCT01321554).Relationship between lenvatinib exposure & PFS was assessed using Kaplan-Meier plots.Parametric survival model(proportional hazard model)with Weibull distribution structure was developed to estimate probability distribution of time from study start to progression as function of covariates including baseline disease characteristics,demographics,lenvatinib exposure,changes in biomarker time profiles,model predicted change from baseline tumor size & change in tumor size time-profiles.Significant(p<0.01)covariates from univariate analysis were added to model simultaneously & significant predictors retained as per backward exclusion criteria(log likelihood ratio test,p-value of 0.001).Data presented are predicted baseline tumor size from the model with Measure Type "Number"estimated using non-linear mixed effects modelling. | PK/PD analysis for PFS was performed for DTC participants who received lenvatinib or placebo in study E7080-G000-303 (NCT01321554) and this current study E7080-G000-211. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | per millimeter (/mm) | Time from the date of randomization to the date of first documentation of PD, or date of death, whichever occurred first up to approximately 3 years 3 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Input Rate Indirect Effect Model Estimate From Base/Final PK/PD Blood Pressure Model | Per the planned analysis, Arms/Groups were combined and population PK/PD analysis for blood pressure was based on lenvatinib and placebo pooled data from this study combined with study E7080-G000-201 (NCT00784303) & study E7080-G000-303 (NCT01321554). The effect of lenvatinib exposure (AUC) at the time of blood pressure assessment on systolic and diastolic blood pressure was tested as a simultaneous indirect model where lenvatinib AUC was linked to the input rate of the indirect effect model by a linear slope factor function. Based on the results from model development, an indirect PK/PD model with a linear effect of lenvatinib exposure on both systolic and diastolic blood pressure was selected as the base model for subsequent univariate analysis. The data presented are the input rate indirect effect model estimate, with Measure Type "Number." They are population PK/PD model predictions and have been estimated using mixed effects non-linear modeling. | For PK/PD analyses of blood pressure, participants received lenvatinib in studies E7080-G000-211, E7080-G000-201 (NCT00784303) and E7080-G000-303 (NCT01321554), with PK information and who had at least one post-baseline evaluation, and participants received placebo in study E7080-G000-303 were included. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | millimeters of mercury per hour | From date of first administration of study drug up to 6 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Drug Effect on Systolic and Diastolic Input Rate Estimates From Base/Final PK/PD Blood Pressure Model | Per the planned analysis, Arms/Groups were combined and population PK/PD analysis for blood pressure was based on lenvatinib and placebo pooled data from this study combined with study E7080-G000-201 (NCT00784303) & study E7080-G000-303 (NCT01321554). The effect of lenvatinib exposure (AUC) at the time of blood pressure assessment on systolic and diastolic blood pressure was tested as a simultaneous indirect model where lenvatinib AUC was linked to the input rate of the indirect effect model by a linear slope factor function. Based on the results from model development, an indirect PK/PD model with a linear effect of lenvatinib exposure on both systolic and diastolic blood pressure was selected as the base model for subsequent univariate analysis. The data presented are the input rate indirect effect model estimate, with Measure Type "Number." They are population PK/PD model predictions and have been estimated using non-linear mixed effects modeling. | For PK/PD analyses of blood pressure, participants received lenvatinib in studies E7080-G000-211, E7080-G000-201 (NCT00784303) and E7080-G000-303 (NCT01321554), with PK information and who had at least one post-baseline evaluation, and participants received placebo in study E7080-G000-303 were included. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | per nanogram*hour per mL*10^6 | From date of first administration of study drug up to 6 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Weight Decrease Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined and a population PK/PD analysis of the relationship between lenvatinib exposure and occurrence of the TEAE weight decreased was based on placebo and lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) and study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE weight decreased and lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, and random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE and a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate) or Grade 3 (severe or medically significant) TEAE were estimated as a function of lenvatinib or exposure. | For PK/PD analysis of the TEAE weight decreased,participants with DTC who received lenvatinib and placebo from studies E7080-G000-211,E7080-G000-201(NCT00784303)and E7080-G000-303 (NCT01321554)with PK information and who had at least 1 postbaseline safety evaluation were included in analysis.Overall number of participants analyzed signifies participants who were evaluable for outcome measure.Number analyzed signifies participants who were evaluable for this outcome measure for given categories. | Posted | Count of Participants | Participants | Up to 3 years 3 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Hypertension Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined & a population PK/PD analysis of the relationship between lenvatinib exposure & occurrence of the TEAE hypertension was based on placebo & lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) & study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE hypertension & lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, & random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE & a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (severe or medically significant) or Grade 4 (life-threatening consequences) TEAE were estimated as a function of lenvatinib or exposure. | For PK/PD analysis of the TEAE hypertension,participants with DTC who received lenvatinib and placebo from studies E7080-G000-211,E7080-G000-201(NCT00784303)and E7080-G000-303 (NCT01321554)with PK information and who had at least 1 postbaseline safety evaluation were included in analysis.Overall number of participants analyzed signifies participants who were evaluable for outcome measure.Number analyzed signifies participants who were evaluable for this outcome measure for given categories. | Posted | Count of Participants | Participants | Up to 3 years 3 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Proteinuria Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined and a population PK/PD analysis of the relationship between lenvatinib exposure and occurrence of the TEAE proteinuria was based on placebo and lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) and study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE proteinuria and lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, and random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE and a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate), or Grade 3 (severe or medically significant) TEAE were estimated as a function of lenvatinib or exposure. | For PK/PD analysis of the TEAE proteinuria,participants with DTC who received lenvatinib and placebo from studies E7080-G000-211,E7080-G000-201(NCT00784303)and E7080-G000-303 (NCT01321554)with PK information and who had at least 1 postbaseline safety evaluation were included in analysis.Overall number of participants analyzed signifies participants who were evaluable for outcome measure.Number analyzed signifies participants who were evaluable for this outcome measure for given categories. | Posted | Count of Participants | Participants | Up to 3 years 3 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Fatigue Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined and a population PK/PD analysis of the relationship between lenvatinib exposure and occurrence of the TEAE fatigue was based on placebo and lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) and study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE fatigue and lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, and random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE and a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate) or Grade 3 (severe or medically significant) TEAE were estimated as a function of lenvatinib or exposure. | For PK/PD analysis of the TEAE fatigue,participants with DTC who received lenvatinib and placebo from studies E7080-G000-211,E7080-G000-201(NCT00784303)and E7080-G000-303 (NCT01321554)with PK information and who had at least 1 postbaseline safety evaluation were included in analysis.Overall number of participants analyzed signifies participants who were evaluable for outcome measure.Number analyzed signifies participants who were evaluable for this outcome measure for given categories. | Posted | Count of Participants | Participants | Up to 3 years 3 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Diarrhea Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined and a population PK/PD analysis of the relationship between lenvatinib exposure and occurrence of the TEAE diarrhea was based on placebo and lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) and study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE diarrhea and lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, and random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE and a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate) or Grade 3 (severe or medically significant) TEAE were estimated as a function of lenvatinib or exposure. | For PK/PD analysis of the TEAE diarrhea,participants with DTC who received lenvatinib and placebo from studies E7080-G000-211,E7080-G000-201(NCT00784303)and E7080-G000-303 (NCT01321554)with PK information and who had at least 1 postbaseline safety evaluation were included in analysis.Overall number of participants analyzed signifies participants who were evaluable for outcome measure.Number analyzed signifies participants who were evaluable for this outcome measure for given categories. | Posted | Count of Participants | Participants | Up to 3 years 3 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Nausea Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined and a population PK/PD analysis of the relationship between lenvatinib exposure and occurrence of the TEAE nausea was based on placebo and lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) and study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE nausea and lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, and random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE and a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate) or Grade 3 (severe or medically significant) TEAE were estimated as a function of lenvatinib or exposure. | For PK/PD analysis of the TEAE nausea,participants with DTC who received lenvatinib and placebo from studies E7080-G000-211,E7080-G000-201(NCT00784303)and E7080-G000-303 (NCT01321554)with PK information and who had at least 1 postbaseline safety evaluation were included in analysis.Overall number of participants analyzed signifies participants who were evaluable for outcome measure.Number analyzed signifies participants who were evaluable for this outcome measure for given categories. | Posted | Count of Participants | Participants | Up to 3 years 3 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Vomiting Stratified by AUC Quartile (Q) Group | Per the planned analysis for this endpoint, Arms/Groups were combined and a population PK/PD analysis of the relationship between lenvatinib exposure and occurrence of the TEAE vomiting was based on placebo and lenvatinib pooled data from this study combined with study E7080-G000-201 (NCT00784303) and study E7080-G000-303 (NCT01321554). The relationship of occurrence probability of different grades of the TEAE vomiting and lenvatinib exposure were evaluated by logistic regression model. The logit model was of the form: sum of intercept, of lenvatinib exposure, effects of covariates were explored, and random effects were used to describe between participant variability. Lenvatinib exposure was AUC based on the dose at the time of event. For each TEAE, probabilities of having no TEAE and a CTCAE Version 4.03 Grade 1 (Mild), Grade 2 (Moderate) or Grade 3 (severe or medically significant) TEAE were estimated as a function of lenvatinib or exposure. | For PK/PD analysis of the TEAE vomiting, participants with DTC who received lenvatinib and placebo from studies E7080-G000-211,E7080-G000-201(NCT00784303)and E7080-G000-303 (NCT01321554)with PK information and who had at least 1 postbaseline safety evaluation were included in analysis. Overall number of participants analyzed signifies participants who were evaluable for outcome measure. Number analyzed signifies participants who were evaluable for this outcome measure for given categories. | Posted | Count of Participants | Participants | Up to 3 years 3 months |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in the Health-Related Quality of Life (HRQoL) Assessed by European Quality of Life (EuroQol) Five-Dimensional, 3-Level (EQ-5D-3L) Index Score and Visual Analogue Scale (VAS) | The EQ-5D-3L is a health profile questionnaire assessing quality of life along 5 dimensions. Participants rate 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranges from 5-15 with "5" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions. EQ-5D-3L also included an EQ visual analogue scale (VAS) that ranges between 100 (best imaginable health) and 0 (worst imaginable health). Decrease from baseline in EQ-5D-3L signifies improvement. Total index EQ-5D-3L summary score was weighted with a range of -0.594 (worst) to 1.0 (best). EQ-5D-3L also included an EQ health utilities index (HUI) where 1 indicated full health while a score of 0 indicated worst health/death. | FAS included all participants randomly assigned to treatment. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 8, 16, and 24 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in the HRQoL Assessed by Functional Assessment of Cancer Therapy-General (FACT-G) Total Score | The FACT-G is a 27-item questionnaire that measures the effect of cancer treatment on quality of life that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being). Each item has a 5-point scale response set (0: not at all; 1: a little bit; 2: somewhat; 3: quite a bit; and 4: very much). The FACT-G total score ranges between 0 and 108. Higher score indicates better quality of life. | FAS included all participants randomly assigned to treatment. | Posted | Mean | Standard Deviation | score on a scale | Baseline, Week 8, 16 and 24 |
|
From date of first administration of study drug up to 28 days after last dose of study drug up to approximately 3 years 3 months
Not provided
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 | Lenvatinib 24 mg | Participants received lenvatinib 24 mg, capsule, orally, once daily in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first (up to 35 months). To maintain blinded treatment assignment, participants received a total of 4 capsules in the form of two 10-mg capsules and one 4-mg capsule containing lenvatinib and one 4-mg placebo capsule. | 11 | 75 | 26 | 75 | 75 | 75 |
| EG001 | Lenvatinib 18 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first (up to 35 months). To maintain blinded treatment assignment, participants received a total of 4 capsules in the form of one 10-mg capsule and two 4-mg capsules containing lenvatinib and one 10-mg placebo capsule. | 19 | 77 | 35 | 77 | 76 | 77 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Thrombotic microangiopathy | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pleuropericarditis | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ventricular fibrillation | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Retinal vascular occlusion | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Impaired gastric emptying | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumatosis intestinalis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Sudden death | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hepatitis toxic | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Abscess limb | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Appendicitis perforated | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Groin abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Septic shock | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Stoma site infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Viral upper respiratory tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Hand fracture | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Post procedural complication | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Subcutaneous haematoma | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Subdural haematoma | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Electrocardiogram abnormal | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Joint ankylosis | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Malignant pleural effusion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Metastases to spine | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Cervical radiculopathy | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Post-traumatic epilepsy | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vocal cord paralysis | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Bronchial obstruction | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Subcutaneous emphysema | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Increased tendency to bruise | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Microcytosis | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Neutrophilia | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Acute coronary syndrome | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Bradycardia | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cardiac failure | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cardiomyopathy | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Coronary artery disease | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cyanosis | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Extrasystoles | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Left ventricular dysfunction | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Myocardial ischaemia | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Palpitations | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Sinus tachycardia | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Supraventricular extrasystoles | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ventricular fibrillation | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Deafness unilateral | Ear and labyrinth disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ear discomfort | Ear and labyrinth disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypoacusis | Ear and labyrinth disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Tinnitus | Ear and labyrinth disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vertigo positional | Ear and labyrinth disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypoparathyroidism | Endocrine disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Inappropriate antidiuretic hormone secretion | Endocrine disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Thyroid haemorrhage | Endocrine disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cataract | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Conjunctival haemorrhage | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dacryostenosis acquired | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dry eye | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Glaucoma | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ocular hyperaemia | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Photopsia | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Retinal tear | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Retinal vascular occlusion | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Abdominal pain lower | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Anal fissure | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Anal incontinence | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Anorectal discomfort | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Apical granuloma | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Chapped lips | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dental caries | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Duodenal ulcer | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Faeces pale | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Gingival bleeding | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Glossitis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Glossodynia | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Lip oedema | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Lip ulceration | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Melaena | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Mouth ulceration | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oesophageal stenosis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oesophagitis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oral discomfort | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oral disorder | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oral dysaesthesia | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Paraesthesia oral | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rectal haemorrhage | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Tongue discolouration | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Tongue discomfort | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Tongue ulceration | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Tooth disorder | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Toothache | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Axillary pain | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Catheter site pain | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Chest discomfort | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Discomfort | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Early satiety | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Facial pain | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Gait disturbance | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Generalised oedema | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperthermia | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Impaired healing | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Induration | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pain | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Temperature intolerance | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Drug hypersensitivity | Immune system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Asymptomatic bacteriuria | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Bacteriuria | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Bronchiolitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Device related infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Eyelid infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Folliculitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Fungal infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Furuncle | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Gastroenteritis viral | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Gingivitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Helicobacter infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Herpes zoster | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Laryngitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Lymph gland infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Oesophageal candidiasis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Oral fungal infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Pyuria | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Rash pustular | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Sialoadenitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Tooth abscess | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Tooth infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Tracheitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Viral infection | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Corneal abrasion | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Facial bones fracture | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Incision site pain | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Ligament sprain | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Limb injury | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Post procedural pulmonary embolism | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Procedural nausea | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Skin abrasion | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Bacterial test positive | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Biopsy prostate normal | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood albumin decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood bilirubin increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood calcium decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood creatine phosphokinase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood glucose increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood potassium increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood pressure increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood thyroid stimulating hormone increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood triglycerides increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood urea increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood uric acid increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Blood urine present | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Creatinine renal clearance decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Ejection fraction decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Electrocardiogram QRS complex prolonged | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Electrocardiogram QT prolonged | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Electrocardiogram ST-T segment abnormal | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Electrocardiogram T wave inversion | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Electrocardiogram abnormal | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Gamma-glutamyltransferase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Glucose urine present | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| International normalised ratio increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Platelet count decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Platelet count increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Tracheal aspiration procedure | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Transaminases increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Troponin I increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Urine ketone body present | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Urine leukocyte esterase positive | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Weight increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| White blood cell count increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| White blood cells urine positive | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Abnormal loss of weight | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Acidosis | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cachexia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dyslipidaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperamylasaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperphosphataemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypoproteinaemia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Metabolic alkalosis | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vitamin B12 deficiency | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Amyotrophy | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Bone pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cervical spinal stenosis | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Coccydynia | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dupuytren's contracture | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypercreatinaemia | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Intervertebral disc displacement | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Joint stiffness | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Joint swelling | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Periarthritis | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Plantar fasciitis | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rotator cuff syndrome | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Sarcopenia | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Malignant pleural effusion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Metastases to bone | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Skin cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Tumour necrosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Uterine leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Amnesia | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Balance disorder | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Carotid artery aneurysm | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Carotid artery stenosis | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cervical radiculopathy | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cognitive disorder | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Disturbance in attention | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dysaesthesia | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Essential tremor | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypogeusia | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Lethargy | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Muscle spasticity | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Neuralgia | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Parkinson's disease | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Presyncope | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Taste disorder | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vocal cord paralysis | Nervous system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Depressed mood | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hallucination | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Irritability | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Libido decreased | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Nervousness | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Thermophobia | Psychiatric disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Chronic kidney disease | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Leukocyturia | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Renal cyst | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Urinary tract obstruction | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Amenorrhoea | Reproductive system and breast disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Breast pain | Reproductive system and breast disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Genital haemorrhage | Reproductive system and breast disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Menstruation irregular | Reproductive system and breast disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Metrorrhagia | Reproductive system and breast disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ovarian cyst | Reproductive system and breast disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pelvic pain | Reproductive system and breast disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Varicocele | Reproductive system and breast disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Atelectasis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Increased upper airway secretion | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Nasal dryness | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Orthopnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pharyngeal inflammation | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pharyngeal swelling | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Sinus pain | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Sputum increased | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Blister | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dermal cyst | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Drug reaction with eosinophilia and systemic symptoms | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ingrowing nail | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ingrown hair | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Ischaemic skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Nail bed bleeding | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Palmoplantar keratoderma | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Plantar erythema | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rash pruritic | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Skin fissures | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Skin haemorrhage | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Skin induration | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Skin reaction | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Skin toxicity | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vitiligo | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Blood pressure fluctuation | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Flushing | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Haemorrhage | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypertensive crisis | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Peripheral venous disease | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Vasculitis | Vascular disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Lymphocytosis | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Macrocytosis | Blood and lymphatic system disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Toxic cardiomyopathy | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Cardiac failure acute | Cardiac disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Eye irritation | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Periorbital oedema | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Swelling of eyelid | Eye disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Gingival pain | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Inguinal hernia | Gastrointestinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Feeling abnormal | General disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| COVID-19 pneumonia | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Abscess oral | Infections and infestations | MedDRA (23.0) | Systematic Assessment |
| |
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Post procedural haematoma | Injury, poisoning and procedural complications | MedDRA (23.0) | Systematic Assessment |
| |
| Electrocardiogram T wave abnormal | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Haemoglobin increased | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Urine analysis abnormal | Investigations | MedDRA (23.0) | Systematic Assessment |
| |
| Hypophagia | Metabolism and nutrition disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Prostate cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (23.0) | Systematic Assessment |
| |
| Calculus urinary | Renal and urinary disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rhinalgia | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Respiratory disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Papule | Skin and subcutaneous tissue disorders | MedDRA (23.0) | Systematic Assessment |
| |
| Tooth extraction | Surgical and medical procedures | MedDRA (23.0) | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eisai Medical Information | Eisai Inc. | 1-888-274-2378 | esi_oncmedinfo@eisai.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 20, 2020 | Dec 7, 2020 | SAP_001.pdf |
| ID | Term |
|---|---|
| D013964 | Thyroid Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D004700 | Endocrine System Diseases |
| D013959 | Thyroid Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C531958 | lenvatinib |
Not provided
Not provided
Not provided
| 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 |
|
| OG001 | Lenvatinib 18 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first (up to 35 months). To maintain blinded treatment assignment, participants received a total of 4 capsules in the form of one 10-mg capsule and two 4-mg capsules containing lenvatinib and one 10-mg placebo capsule. |
|
|
|
|
|
|
| OG001 | Lenvatinib 18 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first (up to 35 months). To maintain blinded treatment assignment, participants received a total of 4 capsules in the form of one 10-mg capsule and two 4-mg capsules containing lenvatinib and one 10-mg placebo capsule. |
|
|
|
|
|
|
|
|
| OG001 | Lenvatinib 18 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first (up to 35 months) in this current study E7080-G000-211. To maintain blinded treatment assignment, participants received a total of 4 capsules in the form of one 10-mg capsule and two 4-mg capsules containing lenvatinib and one 10-mg placebo capsule. |
|
|
| OG001 | Lenvatinib 18 mg | Participants received lenvatinib 18 mg, capsule, orally, once daily in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first (up to 35 months) in this current study E7080-G000-211. To maintain blinded treatment assignment, participants received a total of 4 capsules in the form of one 10-mg capsule and two 4-mg capsules containing lenvatinib and one 10-mg placebo capsule. |
|
|
|
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Lenvatinib or Placebo - All Participants | All participants who received lenvatinib 24 mg or 18 mg or placebo, capsule, orally, once daily in a 28-day treatment cycles until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first in studies E7080-G000-303 (NCT01321554) and this current study (E7080-G000-211). |
|
|
| OG000 |
| Lenvatinib or Placebo - All Participants |
All participants who received lenvatinib 24 mg or 18 mg or placebo, capsule, orally, once daily in a 28-day treatment cycles until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first in studies E7080-G000-303 (NCT01321554) and this current study (E7080-G000-211). |
|
|
| OG000 | Lenvatinib or Placebo - All Participants | All participants who received lenvatinib 24 mg or 18 mg or placebo, capsule, orally, once daily in a 28-day treatment cycles until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first in studies E7080-G000-303 (NCT01321554) and this current study (E7080-G000-211). |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
All participants received lenvatinib 24 mg or 18 mg or placebo, capsule orally, once daily in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first in studies E7080-G000-303 (NCT01321554), E7080-G000-201 (NCT00784303) and this current study (E7080-G000-211) with available pharmacokinetic data.
|
|
|
|
|
|
|
|
|
|
|
|
| OG001 | Lenvatinib 18 mg | Participants initially received lenvatinib 18 mg, capsule, orally, once daily in a 28-day treatment cycle until PD, development of unacceptable toxicity, participant requested to discontinue treatment, withdrew consent or lost to follow-up, until the end of the study, or until study termination by the sponsor, whichever occurred first (up to 35 months). To maintain blinded treatment assignment, participants received a total of 4 capsules in the form of one 10-mg capsule and two 4-mg capsules containing lenvatinib and one 10-mg placebo capsule. |
|
|
|
|