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| ID | Type | Description | Link |
|---|---|---|---|
| jRCT2041200074 | Other Identifier | Japan Registry of Clinical Trials |
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This phase 2, multicenter, two-part, open-label, single-arm study will be conducted in Japan and will evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of pexidartinib in adult participants with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitation and not amenable to improvement with surgery.
This study will consist of 2 parts. In Part 1, pexidartinib 800 mg/day (400 mg twice a day [BID]) will be administered on an empty stomach and tolerability and PK of pexidartinib will be evaluated to determine the initiation of Part 2. In Part 2, pexidartinib 800 mg/day (400 mg BID) will be administered on an empty stomach and efficacy, safety, and PK of pexidartinib will be evaluated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pexidartinib | Experimental | Participants with TGCT who will receive oral pexidartinib 800 mg (400 mg twice daily [BID]). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pexidartinib | Drug | 400 mg twice daily for a total daily dose of 800 mg (each capsule contains 200 mg of pexidartinib for oral administration) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose-limiting Toxicity (DLT) in Part 1 | The number of participants with any-grade DLT treatment-emergent adverse events (TEAEs) were assessed. | Cycle 1, Day 1 to Cycle 1, Day 28 (each cycle is 28 days) |
| Pharmacokinetic Parameter Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1 | Pharmacokinetic parameters were assessed using non-compartmental methods. Cmax is the maximum concentration of pexidartinib and ZAAD-1006a in plasma. | Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hr post-dose of Cycle 1, Day 1 (C1D1) and Predose, 0.5 hr, 1 hr, 2 hr, 4 hr, and 6 hr postdose of Cycle 1, Day 15 (C1D15) (each cycle is 28 days) |
| Pharmacokinetic Parameter Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of Pexidartinib and ZAAD-1006a (AUClast) in Part 1 | Pharmacokinetic parameters were assessed using non-compartmental methods. AUClast is the area under the concentration-time curve from time zero to time of last measurable concentration of pexidartinib and ZAAD-1006a in plasma. | Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hrs post-dose of Cycle 1, Day 1 (C1D1) (each cycle is 28 days) |
| Pharmacokinetic Parameter Area Under the Concentration-Time Curve Up to Infinity of Pexidartinib and ZAAD-1006a (AUCinf) in Part 1 | Pharmacokinetic parameters were assessed using non-compartmental methods. AUCinf is the area under the concentration-time curve up to infinity of pexidartinib and ZAAD-1006a in plasma. | Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hrs post-dose of Cycle 1, Day 1 (C1D1) (each cycle is 28 days) |
| Pharmacokinetic Parameter Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1 | Pharmacokinetic parameters were assessed using non-compartmental methods. Tmax is the time to reach maximum concentration of pexidartinib and ZAAD-1006a in plasma. |
| Measure | Description | Time Frame |
|---|---|---|
| ORR Based on Tumor Volume Score (TVS) in Part 2 | ORR will be assessed by centrally reviewed MRI scan based on TVS. | Week 25 |
| Range of Motion (ROM) in Part 2 | Mean change from baseline in ROM of the affected joint, relative to a reference standard for the same joint will be assessed. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Global Clinical Leader | Daiichi Sankyo | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nagoya University Hospital | Aichi | 466-8560 | Japan | |||
| Kyushu University Hospital |
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A total of 9 participants who met all inclusion criteria and no exclusion criteria were enrolled in the study. These results are based on Part 1 of the study. All safety and pharmacokinetic primary outcome analysis data for Part 1 are reported. Part 2 of the study was not conducted. Eight patients remain in the study and are being followed until study completion. Only the final safety data of the patients who remain on study will be reported at the final database cut (estimated May 31, 2026).
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| ID | Title | Description |
|---|---|---|
| FG000 | Pexidartinib | Participants with TGCT who received oral pexidartinib 800 mg (400 mg twice daily [BID]). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Demographic and baseline characteristics were assessed in the Safety Analysis Set.
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| ID | Title | Description |
|---|---|---|
| BG000 | Pexidartinib | Participants with TGCT who received oral pexidartinib 800 mg (400 mg twice daily [BID]). |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of 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 | Dose-limiting Toxicity (DLT) in Part 1 | The number of participants with any-grade DLT treatment-emergent adverse events (TEAEs) were assessed. | All DLT TEAEs were assessed in the DLT Evaluable Set. | Posted | Count of Participants | Participants | Cycle 1, Day 1 to Cycle 1, Day 28 (each cycle is 28 days) |
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Adverse events were collected from screening to 28 days (+/-7 days) after last dose of study treatment, up to 3 years 7 months (data cut-off date).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pexidartinib | Participants with TGCT who received oral pexidartinib 800 mg (400 mg twice daily [BID]). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hair colour changes | Skin and subcutaneous tissue disorders | MedDRA27.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Contact for Clinical Trial Information | Daiichi Sankyo | 908-992-6400 | CTRinfo@dsi.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 27, 2024 | Dec 18, 2024 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000070779 | Giant Cell Tumor of Tendon Sheath |
| D013586 | Synovitis, Pigmented Villonodular |
| ID | Term |
|---|---|
| D005870 | Giant Cell Tumors |
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C000600259 | pexidartinib |
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| Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hr post-dose of Cycle 1, Day 1 (C1D1) and Predose, 0.5 hr, 1 hr, 2 hr, 4 hr, and 6 hr postdose of Cycle 1, Day 15 (C1D15) (each cycle is 28 days) |
| Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST Version 1.1) in Part 2 | ORR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. | Week 25 |
| Week 25 |
| Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale in Part 2 | Mean change from baseline score in the PROMIS Physical Function Scale will be assessed. | Week 25 |
| Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) in Part 2 | Proportion of responders will be assessed based on the BPI Worst Pain NRS item and analgesic use by BPI-30 definition (ie, 30% or more improvement in average NRS). | Week 25 |
| Best Overall Response (BOR) Based on RECIST Version 1.1 in Part 2 | BOR will be assessed by centrally reviewed magnetic resonance imaging (MRI) scan based on RECIST version 1.1. | Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months |
| BOR Based on TVS in Part 2 | BOR will be assessed by centrally reviewed MRI scan based on TVS. | Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months |
| Duration of Response (DoR) Based on RECIST Version 1.1 in Part 2 | DoR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1. | Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months |
| DoR Based on TVS | DoR will be assessed by centrally reviewed MRI scan based on TVS. | Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months |
| Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events | Baseline up to 28 (+/- 7 days) after last dose, up to approximately 6 years 9 months |
| Fukuoka |
| 812-8582 |
| Japan |
| Kanazawa University Hospital | Ishikawa | 920-8641 | Japan |
| National Hospital Organization Osaka National Hospital | Osaka | 540-0006 | Japan |
| Osaka International Cancer Institute | Osaka | 541-8567 | Japan |
| National Cancer Center Hospital | Tokyo | 104-0045 | Japan |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Primary | Pharmacokinetic Parameter Maximum Concentration of Pexidartinib and ZAAD-1006a (Cmax) in Part 1 | Pharmacokinetic parameters were assessed using non-compartmental methods. Cmax is the maximum concentration of pexidartinib and ZAAD-1006a in plasma. | Pharmacokinetic data were assessed in the Pharmacokinetic Analysis Set. | Posted | Mean | Standard Deviation | ng/mL | Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hr post-dose of Cycle 1, Day 1 (C1D1) and Predose, 0.5 hr, 1 hr, 2 hr, 4 hr, and 6 hr postdose of Cycle 1, Day 15 (C1D15) (each cycle is 28 days) |
|
|
|
| Primary | Pharmacokinetic Parameter Area Under the Concentration-Time Curve From Time Zero to Time of Last Measurable Concentration of Pexidartinib and ZAAD-1006a (AUClast) in Part 1 | Pharmacokinetic parameters were assessed using non-compartmental methods. AUClast is the area under the concentration-time curve from time zero to time of last measurable concentration of pexidartinib and ZAAD-1006a in plasma. | Pharmacokinetic data were assessed in the Pharmacokinetic Analysis Set. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hrs post-dose of Cycle 1, Day 1 (C1D1) (each cycle is 28 days) |
|
|
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| Primary | Pharmacokinetic Parameter Area Under the Concentration-Time Curve Up to Infinity of Pexidartinib and ZAAD-1006a (AUCinf) in Part 1 | Pharmacokinetic parameters were assessed using non-compartmental methods. AUCinf is the area under the concentration-time curve up to infinity of pexidartinib and ZAAD-1006a in plasma. | Pharmacokinetic data were assessed in participants with available data in the Pharmacokinetic Analysis Set. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hrs post-dose of Cycle 1, Day 1 (C1D1) (each cycle is 28 days) |
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|
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| Primary | Pharmacokinetic Parameter Time to Reach Maximum Concentration of Pexidartinib and ZAAD-1006a (Tmax) in Part 1 | Pharmacokinetic parameters were assessed using non-compartmental methods. Tmax is the time to reach maximum concentration of pexidartinib and ZAAD-1006a in plasma. | Pharmacokinetic data were assessed in the Pharmacokinetic Analysis Set. | Posted | Median | Full Range | hours | Predose, 0.5 hours (hr), 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 24 hr post-dose of Cycle 1, Day 1 (C1D1) and Predose, 0.5 hr, 1 hr, 2 hr, 4 hr, and 6 hr postdose of Cycle 1, Day 15 (C1D15) (each cycle is 28 days) |
|
|
|
| Primary | Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST Version 1.1) in Part 2 | ORR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1. Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. | Part 2 of this study was not conducted and efficacy data are not available for reporting. Only the final safety data of patients who remain in the study will be reported at the final database cut (estimated May 31, 2026). | Posted | Week 25 |
|
|
| Secondary | ORR Based on Tumor Volume Score (TVS) in Part 2 | ORR will be assessed by centrally reviewed MRI scan based on TVS. | Part 2 of this study was not conducted and efficacy data are not available for reporting. Only the final safety data of patients who remain in the study will be reported at the final database cut (estimated May 31, 2026). | Posted | Week 25 |
|
|
| Secondary | Range of Motion (ROM) in Part 2 | Mean change from baseline in ROM of the affected joint, relative to a reference standard for the same joint will be assessed. | Part 2 of this study was not conducted and efficacy data are not available for reporting. Only the final safety data of patients who remain in the study will be reported at the final database cut (estimated May 31, 2026). | Posted | Week 25 |
|
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| Secondary | Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function Scale in Part 2 | Mean change from baseline score in the PROMIS Physical Function Scale will be assessed. | Part 2 of this study was not conducted and efficacy data are not available for reporting. Only the final safety data of patients who remain in the study will be reported at the final database cut (estimated May 31, 2026). | Posted | Week 25 |
|
|
| Secondary | Brief Pain Inventory (BPI) Worst Pain Numeric Rating Scale (NRS) in Part 2 | Proportion of responders will be assessed based on the BPI Worst Pain NRS item and analgesic use by BPI-30 definition (ie, 30% or more improvement in average NRS). | Part 2 of this study was not conducted and efficacy data are not available for reporting. Only the final safety data of patients who remain in the study will be reported at the final database cut (estimated May 31, 2026). | Posted | Week 25 |
|
|
| Secondary | Best Overall Response (BOR) Based on RECIST Version 1.1 in Part 2 | BOR will be assessed by centrally reviewed magnetic resonance imaging (MRI) scan based on RECIST version 1.1. | Part 2 of this study was not conducted and efficacy data are not available for reporting. Only the final safety data of patients who remain in the study will be reported at the final database cut (estimated May 31, 2026). | Posted | Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months |
|
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| Secondary | BOR Based on TVS in Part 2 | BOR will be assessed by centrally reviewed MRI scan based on TVS. | Part 2 of this study was not conducted and efficacy data are not available for reporting. Only the final safety data of patients who remain in the study will be reported at the final database cut (estimated May 31, 2026). | Posted | Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months |
|
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| Secondary | Duration of Response (DoR) Based on RECIST Version 1.1 in Part 2 | DoR will be assessed by centrally reviewed MRI scan based on RECIST version 1.1. | Part 2 of this study was not conducted and efficacy data are not available for reporting. Only the final safety data of patients who remain in the study will be reported at the final database cut (estimated May 31, 2026). | Posted | Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months |
|
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| Secondary | DoR Based on TVS | DoR will be assessed by centrally reviewed MRI scan based on TVS. | Part 2 of this study was not conducted and efficacy data are not available for reporting. Only the final safety data of patients who remain in the study will be reported at the final database cut (estimated May 31, 2026). | Posted | Post Week 25 visit or following discontinuation from Part 2 of the study (whichever occurs first), up to approximately 1 year 6 months |
|
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| Secondary | Number of Participants Reporting Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events | Not Posted | May 2027 | Baseline up to 28 (+/- 7 days) after last dose, up to approximately 6 years 9 months | Participants |
| 0 |
| 9 |
| 0 |
| 9 |
| 9 |
| 9 |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA27.1 | Systematic Assessment |
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| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA27.1 | Systematic Assessment |
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| Eczema | Skin and subcutaneous tissue disorders | MedDRA27.1 | Systematic Assessment |
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| Skin discolouration | Skin and subcutaneous tissue disorders | MedDRA27.1 | Systematic Assessment |
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| Aspartate aminotransferase increased | Investigations | MedDRA27.1 | Systematic Assessment |
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| Alanine aminotransferase increased | Investigations | MedDRA27.1 | Systematic Assessment |
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| Blood lactate dehydrogenase increased | Investigations | MedDRA27.1 | Systematic Assessment |
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| Gamma-glutamyltransferase increased | Investigations | MedDRA27.1 | Systematic Assessment |
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| Blood alkaline phosphatase increased | Investigations | MedDRA27.1 | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA27.1 | Systematic Assessment |
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| Blood creatinine phosphokinase increased | Investigations | MedDRA27.1 | Systematic Assessment |
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| Blood creatinine increased | Investigations | MedDRA27.1 | Systematic Assessment |
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| Neutrophil count decreased | Investigations | MedDRA27.1 | Systematic Assessment |
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| Amylase increased | Investigations | MedDRA27.1 | Systematic Assessment |
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| Blood cholesterol increased | Investigations | MedDRA27.1 | Systematic Assessment |
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| Weight decreased | Investigations | MedDRA27.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA27.1 | Systematic Assessment |
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| Face oedema | General disorders | MedDRA27.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA27.1 | Systematic Assessment |
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| COVID-19 | Infections and infestations | MedDRA27.1 | Systematic Assessment |
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| Norovirus infection | Infections and infestations | MedDRA27.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA27.1 | Systematic Assessment |
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| Anaemia | Blood and lymphatic system disorders | MedDRA27.1 | Systematic Assessment |
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| Eosinophilia | Blood and lymphatic system disorders | MedDRA27.1 | Systematic Assessment |
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| Leukopenia | Blood and lymphatic system disorders | MedDRA27.1 | Systematic Assessment |
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| Neutropenia | Blood and lymphatic system disorders | MedDRA27.1 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA27.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA27.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA27.1 | Systematic Assessment |
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| Hepatic function abnormal | Hepatobiliary disorders | MedDRA27.1 | Systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA27.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA27.1 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA27.1 | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA27.1 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA27.1 | Systematic Assessment |
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| D009369 | Neoplasms |
| D013585 | Synovitis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D052256 | Tendinopathy |
| D009135 | Muscular Diseases |
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| ZAAD-1006a, C1D1 |
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| ZAAD-1006a, C1D15 |
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| ZAAD-1006a, C1D1 |
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| ZAAD-1006a, C1D15 |
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