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| Name | Class |
|---|---|
| Medarex | INDUSTRY |
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The purpose of this clinical research study is to learn the pharmacokinetics of Ipilimumab when combined with Paclitaxel/Carboplatin or Dacarbazine
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A | Active Comparator |
| |
| Arm B | Active Comparator |
| |
| Arm C | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ipilimumab | Drug | Solution, intravenous, 10mg/kg, every 3 weeks in the induction phase, up to 4 doses in the induction phase, 48 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population | Cmax=micrograms per milliliter (µg/mL): drug concentration versus time for ipilimumab (Day 43) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma by Enzyme-linked Immunosorbent Assay (ELISA); lower level of quantitation (LLOQ)=0.8 µg/mL; upper limit of quantitation (ULOQ)=25.6 µg/mL; Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; from Day 162 on every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined using liquid chromatography tandem mass spectrometry (LC/MS/MS) detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography atmospheric pressure ionization (API) tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose. | Day 1 (0 h) to Day 43 |
| Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population | AUC=micrograms*hour(h) per mL (µg*h/mL): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose. | Day 1 (0 h) to Day 43 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population | Tmax reported in hours (h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Angeles Clinic & Research Inst. | Los Angeles | California | 90025 | United States | ||
| H Lee Moffit Cancer Cnt And Res Inst |
72 enrolled; 59 randomized and treated with study drug. Reasons for non-randomization: 7 no longer met study criteria; 3 withdrew consent; 1 had target lesion <1 cm; 1 had screening magnetic resonance imaging (MRI) showed brain metastases; 1 had adverse event.
17 February 2009 study initiated; last patient, last visit (LPLV) 30 October 2012.
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| ID | Title | Description |
|---|---|---|
| FG000 | Paclitaxel, Carboplatin, Ipilimumab | Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure. |
| FG001 | Dacarbazine, Ipilimumab | Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure. |
| FG002 | Ipilimumab | Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All randomized and treated participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Paclitaxel, Carboplatin, Ipilimumab | Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure. |
| 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 | Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population | Cmax=micrograms per milliliter (µg/mL): drug concentration versus time for ipilimumab (Day 43) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma by Enzyme-linked Immunosorbent Assay (ELISA); lower level of quantitation (LLOQ)=0.8 µg/mL; upper limit of quantitation (ULOQ)=25.6 µg/mL; Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; from Day 162 on every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined using liquid chromatography tandem mass spectrometry (LC/MS/MS) detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography atmospheric pressure ionization (API) tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose. | N=participants who received study drug and with adequate Pharmacokinetic (PK) profiles. N is presented for each study drug in each category below. Day 1=paclitaxel/carboplatin or Day 1=dacarbazine; Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg/mL |
Day 1 up to last patient last visit (LPLV) 30 October 2012
Participants continue in the study until disease progression, toxicities requiring discontinuation, withdrawal of consent, or study closure.
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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 | Paclitaxel, Carboplatin, Ipilimumab | Induction Phase: Participant received paclitaxel 175 mg/m^2 intravenously (IV) by a 3-hour infusion and carboplatin IV by a 30-minute infusion) on Day 1 (Week 1, Day 1) and ipilimumab 10 mg/kg IV administered on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10, and paclitaxel/carboplatin were administered every 3 weeks (Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the paclitaxel and then carboplatin infusions. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthenia | General disorders | MedDRA 15.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Autoimmune disorder | Immune system disorders | MedDRA 15.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Bristol-Myers Squibb Study Director | Bristol-Myers Squibb | Clinical.Trials@bms.com |
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| ID | Term |
|---|---|
| D000074324 | Ipilimumab |
| D016190 | Carboplatin |
| D017239 | Paclitaxel |
| C089957 | BMS 181339 |
| D003606 | Dacarbazine |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Carboplatin | Drug | Solution, intravenous, Area Under the Concentration Time Curve=6, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks |
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| Paclitaxel | Drug | Solution, intravenous, 175 mg/m2, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks |
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|
| Dacarbazine | Drug | Solution, intravenous, 850 mg/m2, every 3 weeks in the induction phase, up to 8 doses in the induction phase, 48 weeks |
|
| Day 1 (0 h) to Day 43 |
| Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population | T(HALF) reported in hours (h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose. | Day 1 (0 h) to Day 43 |
| Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population | CLT reported in milliliters/hour (mL/h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.. | Day 1 (0 h) to Day 43 |
| Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population | Vss reported in liters(L): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose. | Day 1 (0 h) to Day 43 |
| Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants | Assessments for antitumor activity by physical exam and routine anatomic imaging were at Week 12 and confirmatory imaging at Weeks 16, 20, and 24. Participants with resected index or new lesions were considered progressed in their disease. Complete Response (CR): Complete disappearance of all index lesions; Partial Response (PR): Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions, in the absence of Complete Response; Stable Disease (SD): Does not meet criteria for complete or partial response, in the absence of progressive disease. Participants with PR or CR that was not confirmed after at least 4 weeks are scored as SD unless they have new primary lesions; Progressive Disease: At least 25% increase in the sum of products of all index lesions and/or the appearance of any new lesion(s). Unknown=the participants overall response was not known. | Day 1 to Week 48 |
| Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants | Assessments: Weeks 12, 16, 20, and 24. Participants with resected index or new lesions considered progressed in their disease. The immune-related (ir) response criteria (irRC) represents further modifications of mWHO criteria reflecting clinical experience with ipilimumab in which objective and durable responses (as per mWHO) were observed in participants following progression and without intervening alternative anti-cancer therapy. Immune-related (ir)Complete Response (irCR): Complete disappearance of all index lesions; ir Partial Response (irPR): Decrease, relative to baseline, of 50% or greater in sum of products of the two largest perpendicular diameters of all index and all new measurable lesions, in the absence of irCR; ir Stable Disease (irSD): Does not meet criteria for irCR or irPR, in the absence of progressive disease (PD); ir PD: At least 25% increase in Tumor Burden compared to sum of product diameters (SPD) at nadir. ir Unknown=participants overall response not known. | Day 1 to Week 48 |
| Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants | Number of participants with an objective response to treatment excluded participants with a best overall response (BOR) of Stable Disease (SD). Disease control is non-progression of disease while on treatment. A participant was considered to have achieved disease control if he/she had a BOR of CR, PR, or SD in the absence of resected index lesions or new lesions while the participant was considered to have an objective response to treatment in he/she had a BOR of CR or PR in the absence of resected index lesions or new lesions. | Day 1 to Week 48 |
| Number of Participants With Adverse Events, Serious Adverse Events, Deaths, and Discontinuation Due to Adverse Events From Day 1 to Week 48 - All Treated Population | Adverse events (AEs) and Serious AEs (SAEs) were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events version 3.0. Week 48 database lock was 27 July 2010. | Day 1 to Week 48 |
| Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population | Absolute lymphocyte counts were obtained from routine hematology panels from 28 days prior to the first treatment with any study medication through the end of the Induction-Dosing Period and were reported as number*10^3 cells per micro liter (x10^3 c/µL). | Day to Week 12 |
| Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population | Blood pressure was obtained while the participant was sitting down and was measured in millimeters of mercury (mmHg). During the induction phase blood pressure was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Orthostatic blood pressure was to be measured when clinically indicated (for example, participant was experiencing lightheadedness, dizziness, syncope). Blood pressures were recorded at Weeks 1, 4, 7, 10,13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase. | Day 1 to Week 48 |
| Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population | Pulse rate was obtained while the participant was sitting down and measured in beats per minute (bpm). During the induction phase pulse rate was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Pulse rate was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase. | Day 1 to Week 48 |
| Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population | Respiration rate was obtained while the participant was sitting down and measured in breaths per minute (bpm). During the induction phase respiration rate was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Respiration rate was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase. | Day 1 to Week 48 |
| Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population | Temperature was obtained while the participant was sitting down and was measured in degrees Fahrenheit (F). During the induction phase this vital sign was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Temperature was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population | Hemoglobin was measured in grams per deciliter (g/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 10.0 - less than (<) lower limit of normal (LLN); GRADE (2): 8.0 - < 10.0; GRADE (3): 6.5 - < 8.0; GRADE (4): < 6.5 | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population | Leukocytes are measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade. GRADE (1): 3.0 - < LLN; GRADE (2): 2.0 - < 3.0; GRADE (3): 1.0 - < 2.0; GRADE (4): < 1.0. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population | Lymphocytes (absolute) were measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade. GRADE (1): 0.8 - < 1.5; GRADE (2): 0.5 - < 0.8; GRADE (3): 0.2 - < 0.5; GRADE (4): < 0.2 | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population | Neutrophils (absolute) are measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 1.5 - < 2.0; GRADE (2): 1.0 - < 1.5; GRADE (3): 0.5 - < 1.0; GRADE (4): < 0.5 | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population | Neutrophils plus bands (absolute) were measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 1.5 - < 2.0; GRADE (2): 1.0 - < 1.5; GRADE (3): 0.5 - < 1.0; GRADE (4): < 0.5. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population | Platelets were measured as *10^9 cells per liter (c/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 75.0 - < LLN; GRADE (2): 50.0 - < 75.0; GRADE (3): 25.0 - < 50.0; GRADE (4): < 25.0. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population | ALT was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population | AST was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population | Albumin was measured in grams per deciliter (g/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): < LLN - 3.0; GRADE (2): < 3.0 - 2.0; GRADE (3): < 2.0 g/dL. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population | Alkaline Phosphatase was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population | Total Bilirubin was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * upper limits of normal (ULN); GRADE (2): > 1.5 - 3.0 * ULN; GRADE (3): > 3.0 - 10.0 * ULN; GRADE (4): > 10.0 * ULN. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population | Serum potassium was measured as milliequivalents per liter (mEq/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 3.0 - < LLN OR > ULN - 5.5;; GRADE (2): > 5.5 - 6.0; GRADE (3): 2.5 - < 3.0 > 6.0 - 7.0; GRADE (4): < 2.5 mEq/L. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population | Amylase was measured as units per liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * upper limits of normal (ULN); GRADE (2): > 1.5 - 2.0 * ULN; GRADE (3): > 2.0 - 5.0 * ULN; GRADE (4): > 5.0 * ULN. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population | Total Calcium was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 8.0 - < LLN OR > ULN - 11.5; GRADE (2): 7.0 - < 8.0 > 11.5 - 12.5; GRADE (3): 6.0 - < 7.0 > 12.5 - 13.5; GRADE (4): < 6.0 > 13.5 mg/dL. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population | Total Lipase (as measured with a turbidimetric assay) was measured as units per liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * ULN; GRADE (2): > 1.5 - 2.0 * ULN; GRADE (3): > 2.0 - 5.0 * ULN; GRADE (4): > 5.0 X ULN. | Day 1 to Week 48 |
| Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population | Uric acid was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 * ULN - 10.0; GRADE (4): > 10.0 mg/dL. | Day 1 to Week 48 |
| Tampa |
| Florida |
| 33612 |
| United States |
| Memorial Sloan Kettering Cancer Center | New York | New York | 10021 | United States |
| Blumenthal Cancer Center, Carolinas Medical Center | Charlotte | North Carolina | 28204 | United States |
| Disease Progression |
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| Study Drug Toxicity |
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| Withdrawal by Subject |
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| BG001 | Dacarbazine, Ipilimumab | Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure. |
| BG002 | Ipilimumab | Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure. |
| BG003 | Total | Total of all reporting groups |
| 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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| Region of Enrollment | Number | participants |
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| Eastern Cooperative Oncology Group (ECOG) | ECOG performance: 0= Fully active, able to carry on all pre-disease performance without restriction;1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2=Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or Chair; 5=Dead | Number | participants |
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| Number of Target Lesions | Number of participants with 1, 2, 3, 4, or greater than or equal to (>=) 5 lesions which were targeted for the study. | Number | Participants |
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| Day 1 (0 h) to Day 43 |
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| Secondary | Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population | Tmax reported in hours (h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.. | N=participants who received study drug and with adequate PK profiles. N is presented for each study drug in each category below. Day 1=paclitaxel/carboplatin or Day 1=dacarbazine; Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine. | Posted | Median | Full Range | h | Day 1 (0 h) to Day 43 |
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| Secondary | Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population | T(HALF) reported in hours (h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose. | N=participants who received study drug and with adequate PK profiles. N is presented for each study drug in each category below. Day 1=paclitaxel/carboplatin or Day 1=dacarbazine; Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine. | Posted | Mean | Standard Deviation | h | Day 1 (0 h) to Day 43 |
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| Secondary | Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population | CLT reported in milliliters/hour (mL/h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.. | N=participants who received study drug and with adequate PK profiles. N is presented for each study drug in each category below. Day 1=paclitaxel/carboplatin or Day 1=dacarbazine; Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine. | Posted | Geometric Mean | Geometric Coefficient of Variation | mL/h | Day 1 (0 h) to Day 43 |
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| Primary | Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population | AUC=micrograms*hour(h) per mL (µg*h/mL): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose. | N=participants who received study drug and with adequate PK profiles. N is presented for each study drug in each category below. Day 1=paclitaxel/carboplatin or Day 1=dacarbazine; Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine. | Posted | Geometric Mean | Geometric Coefficient of Variation | µg*h/mL | Day 1 (0 h) to Day 43 |
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| Secondary | Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population | Vss reported in liters(L): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose. | N=participants who received study drug and with adequate PK profiles. N is presented for each study drug in each category below. Day 43=ipilimumab+paclitaxel/carboplatin or Day 43=ipilimumab+dacarbazine. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | Day 1 (0 h) to Day 43 |
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| Secondary | Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants | Assessments for antitumor activity by physical exam and routine anatomic imaging were at Week 12 and confirmatory imaging at Weeks 16, 20, and 24. Participants with resected index or new lesions were considered progressed in their disease. Complete Response (CR): Complete disappearance of all index lesions; Partial Response (PR): Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions, in the absence of Complete Response; Stable Disease (SD): Does not meet criteria for complete or partial response, in the absence of progressive disease. Participants with PR or CR that was not confirmed after at least 4 weeks are scored as SD unless they have new primary lesions; Progressive Disease: At least 25% increase in the sum of products of all index lesions and/or the appearance of any new lesion(s). Unknown=the participants overall response was not known. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants | Assessments: Weeks 12, 16, 20, and 24. Participants with resected index or new lesions considered progressed in their disease. The immune-related (ir) response criteria (irRC) represents further modifications of mWHO criteria reflecting clinical experience with ipilimumab in which objective and durable responses (as per mWHO) were observed in participants following progression and without intervening alternative anti-cancer therapy. Immune-related (ir)Complete Response (irCR): Complete disappearance of all index lesions; ir Partial Response (irPR): Decrease, relative to baseline, of 50% or greater in sum of products of the two largest perpendicular diameters of all index and all new measurable lesions, in the absence of irCR; ir Stable Disease (irSD): Does not meet criteria for irCR or irPR, in the absence of progressive disease (PD); ir PD: At least 25% increase in Tumor Burden compared to sum of product diameters (SPD) at nadir. ir Unknown=participants overall response not known. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants | Number of participants with an objective response to treatment excluded participants with a best overall response (BOR) of Stable Disease (SD). Disease control is non-progression of disease while on treatment. A participant was considered to have achieved disease control if he/she had a BOR of CR, PR, or SD in the absence of resected index lesions or new lesions while the participant was considered to have an objective response to treatment in he/she had a BOR of CR or PR in the absence of resected index lesions or new lesions. | Randomized Population includes all participants randomized to a treatment arm | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants With Adverse Events, Serious Adverse Events, Deaths, and Discontinuation Due to Adverse Events From Day 1 to Week 48 - All Treated Population | Adverse events (AEs) and Serious AEs (SAEs) were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events version 3.0. Week 48 database lock was 27 July 2010. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population | Absolute lymphocyte counts were obtained from routine hematology panels from 28 days prior to the first treatment with any study medication through the end of the Induction-Dosing Period and were reported as number*10^3 cells per micro liter (x10^3 c/µL). | Pharmacodynamic Population: All treated participants with one unambiguous date of first dose; and at least 1 ALC evaluation during the induction-dosing period. For each of these participants, all ALC evaluations from 28 days prior to first dose of any study medication to the end of the induction dosing are included. period. | Posted | Mean | 95% Confidence Interval | 10^3 cells/µL | Day to Week 12 |
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| Secondary | Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population | Blood pressure was obtained while the participant was sitting down and was measured in millimeters of mercury (mmHg). During the induction phase blood pressure was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Orthostatic blood pressure was to be measured when clinically indicated (for example, participant was experiencing lightheadedness, dizziness, syncope). Blood pressures were recorded at Weeks 1, 4, 7, 10,13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase. | Treated participants received at least one dose of a study drug. N=number of treated participants who also had blood pressure value available for analysis. | Posted | Mean | Standard Deviation | mmHg | Day 1 to Week 48 |
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| Secondary | Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population | Pulse rate was obtained while the participant was sitting down and measured in beats per minute (bpm). During the induction phase pulse rate was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Pulse rate was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase. | Treated participants received at least one dose of a study drug. N=number of treated participants who also had a Pulse rate value available for analysis. | Posted | Mean | Standard Deviation | bpm | Day 1 to Week 48 |
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| Secondary | Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population | Respiration rate was obtained while the participant was sitting down and measured in breaths per minute (bpm). During the induction phase respiration rate was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Respiration rate was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase. | Treated participants received at least one dose of a study drug. N=number of treated participants who also had a Respiration rate value available for analysis. | Posted | Mean | Standard Deviation | bpm | Day 1 to Week 48 |
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| Secondary | Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population | Temperature was obtained while the participant was sitting down and was measured in degrees Fahrenheit (F). During the induction phase this vital sign was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Temperature was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase. | Treated participants received at least one dose of a study drug. N=number of treated participants who also had a temperature value available for analysis. | Posted | Mean | Standard Deviation | degrees F | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population | Hemoglobin was measured in grams per deciliter (g/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 10.0 - less than (<) lower limit of normal (LLN); GRADE (2): 8.0 - < 10.0; GRADE (3): 6.5 - < 8.0; GRADE (4): < 6.5 | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population | Leukocytes are measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade. GRADE (1): 3.0 - < LLN; GRADE (2): 2.0 - < 3.0; GRADE (3): 1.0 - < 2.0; GRADE (4): < 1.0. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population | Lymphocytes (absolute) were measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade. GRADE (1): 0.8 - < 1.5; GRADE (2): 0.5 - < 0.8; GRADE (3): 0.2 - < 0.5; GRADE (4): < 0.2 | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population | Neutrophils (absolute) are measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 1.5 - < 2.0; GRADE (2): 1.0 - < 1.5; GRADE (3): 0.5 - < 1.0; GRADE (4): < 0.5 | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population | Neutrophils plus bands (absolute) were measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 1.5 - < 2.0; GRADE (2): 1.0 - < 1.5; GRADE (3): 0.5 - < 1.0; GRADE (4): < 0.5. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population | Platelets were measured as *10^9 cells per liter (c/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 75.0 - < LLN; GRADE (2): 50.0 - < 75.0; GRADE (3): 25.0 - < 50.0; GRADE (4): < 25.0. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population | ALT was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population | AST was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population | Albumin was measured in grams per deciliter (g/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): < LLN - 3.0; GRADE (2): < 3.0 - 2.0; GRADE (3): < 2.0 g/dL. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population | Alkaline Phosphatase was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population | Total Bilirubin was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * upper limits of normal (ULN); GRADE (2): > 1.5 - 3.0 * ULN; GRADE (3): > 3.0 - 10.0 * ULN; GRADE (4): > 10.0 * ULN. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population | Serum potassium was measured as milliequivalents per liter (mEq/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 3.0 - < LLN OR > ULN - 5.5;; GRADE (2): > 5.5 - 6.0; GRADE (3): 2.5 - < 3.0 > 6.0 - 7.0; GRADE (4): < 2.5 mEq/L. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population | Amylase was measured as units per liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * upper limits of normal (ULN); GRADE (2): > 1.5 - 2.0 * ULN; GRADE (3): > 2.0 - 5.0 * ULN; GRADE (4): > 5.0 * ULN. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population | Total Calcium was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 8.0 - < LLN OR > ULN - 11.5; GRADE (2): 7.0 - < 8.0 > 11.5 - 12.5; GRADE (3): 6.0 - < 7.0 > 12.5 - 13.5; GRADE (4): < 6.0 > 13.5 mg/dL. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
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| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population | Total Lipase (as measured with a turbidimetric assay) was measured as units per liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * ULN; GRADE (2): > 1.5 - 2.0 * ULN; GRADE (3): > 2.0 - 5.0 * ULN; GRADE (4): > 5.0 X ULN. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
|
|
|
| Secondary | Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population | Uric acid was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 * ULN - 10.0; GRADE (4): > 10.0 mg/dL. | Treated participants received at least one dose of a study drug. | Posted | Number | participants | Day 1 to Week 48 |
|
|
|
| 12 |
| 20 |
| 20 |
| 20 |
| EG001 | Dacarbazine, Ipilimumab | Induction Phase: Participant received dacarbazine 850 mg/m^2 IV by a 1-hour infusion on Day 1 (Week 1, Day 1) and ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes on Day 3 (Week 1, Day 3). Ipilimumab was administered at Weeks 4, 7, and 10 and dacarbazine at Weeks 4, 7, 10, 13, 16, 19, and 22), with participants receiving the ipilimumab infusion first, followed by the dacarbazine infusion. A maximum of 8 doses of chemotherapy was permitted. Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure. | 10 | 19 | 19 | 19 |
| EG002 | Ipilimumab | Induction Phase: Participant received ipilimumab at a dose of 10 mg/kg IV administered over 90 minutes every 3 weeks for up to 4 doses (Week 1 Day 1, and Weeks 4, 7, and 10). Maintenance Phase: Ipilimumab was administered at a dose of 10 mg/kg every 12 Weeks, beginning at Week 24, until disease progression, study drug-associated toxicity, withdrawal of consent or study closure. | 14 | 20 | 20 | 20 |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypopituitarism | Endocrine disorders | MedDRA 15.1 | Systematic Assessment |
|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Malignant pleural effusion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Mental status changes | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Metastases to skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
|
| Meningitis aseptic | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Radiation necrosis | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Autoimmune hepatitis | Hepatobiliary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Autoimmune pancreatitis | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Erythema nodosum | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Metastatic malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Supraventricular tachycardia | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Sepsis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Seroma | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Failure to thrive | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Haematemesis | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Metastases to abdominal cavity | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Metastasis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Optic neuritis | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Peripheral motor neuropathy | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Psychotic disorder | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Renal failure | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Bacteraemia | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Bile duct obstruction | Hepatobiliary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pancytopenia | Blood and lymphatic system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Renal failure acute | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | MedDRA 15.1 | Systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Generalised oedema | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Gingival inflammation | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypopituitarism | Endocrine disorders | MedDRA 15.1 | Systematic Assessment |
|
| Incision site complication | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Neurodermatitis | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Oesophageal pain | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Procedural headache | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Rocky mountain spotted fever | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Urinary retention | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Abdominal hernia | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Amylase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Bacterial infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Discomfort | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Generalised erythema | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Haemorrhoidal haemorrhage | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Oral pain | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Radial nerve palsy | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Rib fracture | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
|
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Spinal pain | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Anal fissure | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Bladder pain | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Blood corticotrophin decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Blood testosterone decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Body tinea | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Groin pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA 15.1 | Systematic Assessment |
|
| Laceration | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Libido decreased | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Mass | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Movement disorder | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Ocular discomfort | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Oesophagitis | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Panic attack | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Photophobia | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Pulmonary haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Renal pain | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Seborrhoeic dermatitis | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Sinus headache | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Staphylococcal infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Visual impairment | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Autoimmune hepatitis | Hepatobiliary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Blood phosphorus decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Candidiasis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Cyanosis | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Diverticulitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Eye pain | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Faecal incontinence | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Flat affect | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Menstruation irregular | Reproductive system and breast disorders | MedDRA 15.1 | Systematic Assessment |
|
| Musculoskeletal discomfort | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Mydriasis | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Nephrolithiasis | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Nodule | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Olfactory nerve disorder | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Scar | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Seborrhoeic keratosis | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Tinea cruris | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Tinea pedis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Uveitis | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Waist circumference increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Weight increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Ataxia | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Early satiety | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Hyperbilirubinaemia | Hepatobiliary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Muscle haemorrhage | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Night sweats | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Onychomycosis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pruritus generalised | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Salmonellosis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Skin exfoliation | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Sleep disorder | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Vitiligo | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA 15.1 | Systematic Assessment |
|
| Blood cortisol decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Diplopia | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Gait disturbance | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Gout | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Infusion site pain | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Lentigo maligna | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Malignant ascites | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Mucous membrane disorder | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Papule | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Periorbital oedema | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Rash generalised | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Actinic keratosis | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Angiosarcoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Bartholin's cyst | Reproductive system and breast disorders | MedDRA 15.1 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Colitis | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Deep vein thrombosis | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Gastrointestinal pain | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypophysitis | Endocrine disorders | MedDRA 15.1 | Systematic Assessment |
|
| Intervertebral disc degeneration | Musculoskeletal and connective tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Lymphoedema | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
|
| Melanocytic naevus | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Mouth haemorrhage | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Photopsia | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 15.1 | Systematic Assessment |
|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 15.1 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Wound complication | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Adrenal insufficiency | Endocrine disorders | MedDRA 15.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Auricular perichondritis | Ear and labyrinth disorders | MedDRA 15.1 | Systematic Assessment |
|
| Blood uric acid increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Catheter site discharge | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 15.1 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Eye inflammation | Eye disorders | MedDRA 15.1 | Systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hemiparesis | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hyperalbuminaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Hypovolaemia | Metabolism and nutrition disorders | MedDRA 15.1 | Systematic Assessment |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Mechanical urticaria | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Occult blood positive | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Odynophagia | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Oxygen saturation decreased | Investigations | MedDRA 15.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 15.1 | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Temperature intolerance | General disorders | MedDRA 15.1 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 15.1 | Systematic Assessment |
|
| Tooth abscess | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 15.1 | Systematic Assessment |
|
| Xerosis | General disorders | MedDRA 15.1 | Systematic Assessment |
|
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D014226 | Triazenes |
| D007093 | Imidazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
|
| Tmax of Paclitaxel (Day 43) N=14, 0, 0 |
|
| Tmax of Dacarbazine (Day 1) N=0, 18, 0 |
|
| Tmax of Dacarbazine (Day 43) N=0, 15, 0 |
|
| Tmax of AIC (Day 1) N=0, 19 0 |
|
| Tmax of AIC (Day 43) N=0, 16, 0 |
|
|
| T(HALF) of Paclitaxel (Day 43) N=14, 0, 0 |
|
| T(HALF) of Dacarbazine (Day 1) N=0, 19, 0 |
|
| T(HALF) of Dacarbazine (Day 43) N=0, 16, 0 |
|
| T(HALF) of AIC (Day 1) N=0, 18, 0 |
|
| T(HALF) of AIC (Day 43) N=0, 16, 0 |
|
|
| CLT of Paclitaxel (Day 43) N=14, 0, 0 |
|
| CLT of Dacarbazine (Day 1) N=0, 19, 0 |
|
| CLT of Dacarbazine (Day 43) N=0, 16, 0 |
|
| CLT of AIC (Day 1) N=0, 19, 0 |
|
| CLT of AIC (Day 43) N=0, 17, 0 |
|
|
| AUC(INF) of Paclitaxel (Day 43) N=14, 0, 0 |
|
| AUC(INF) of Dacarbazine (Day 1) N=0, 19, 0 |
|
| AUC(INF) of Dacarbazine (Day 43) N=0, 16, 0 |
|
| AUC(INF) of AIC (Day 1) N=0, 18, 0 |
|
| AUC(INF) of AIC (Day 43) N=0, 16, 0 |
|
| Estimated effect of ipilimumab on dacarbazine AUC(INF). Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination (Day 43) relative to dacarbazine alone (Day 1). | Mixed Models Analysis | A general linear mixed model was applied to dacarbazine log[AUC(INF)] using study day as a fixed effect. | Adjusted geometric mean ratio | 0.912 | 2-Sided | 90 | 0.757 | 1.099 | No | Superiority or Other |
| Estimated effect of ipilimumab on AUC(INF) for AIC. Point estimates and 90% confidence intervals (CIs) for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination (Day 43) relative to dacarbazine alone (Day 1). | Mixed Models Analysis | A general linear mixed model was applied to active metabolite AIC log[AUC(INF)] using study day as a fixed effect. | Adjusted geometric mean ratio | 0.970 | 2-Sided | 90 | 0.891 | 1.056 | No | Superiority or Other |
| Estimated effect of paclitaxel/carboplatin on ipilimumab AUC: linear model was applied to ipilimumab log(AUC(0-21d)) data from Week 7 (Day 43) PK measurements in first and third arms with treatment arm as a fixed effect. Point estimates and 90% CIs for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the 3 drug combination relative to ipilimumab alone. | linear model | treatment arm as fixed effect | Adjusted geometric mean ratio | 0.934 | 2-Sided | 90 | 0.768 | 1.136 | No | Superiority or Other |
| Estimated effect of dacarbazine on ipilimumab AUC: linear model was applied to ipilimumab log(AUC(0-21d)) data from Week 7 (Day 43) PK measurements in second and third arms with treatment arm as a fixed effect. Point estimates and 90% CIs for means and differences between means on the log scale were exponentiated to obtain estimates for geometric means and ratio of geometric means on the original scale for the dacarbazine, ipilimumab combination relative to ipilimumab alone. | linear model | treatment arm as a fixed effect | Adjusted geometric mean ratio | 0.982 | 2-Sided | 90 | 0.7981 | 1.208 | No | Superiority or Other |
|
| Vss of Dacarbazine (Day 43) N=0, 16, 0 |
|
| Vss of AIC (Day 1) N=0, 17, 0 |
|
| Title | Measurements |
|---|---|
|
| Stable Disease |
|
| Progressive Disease |
|
| Unknown |
|
| Title | Measurements |
|---|---|
|
| ir Stable Disease |
|
| ir Progressive Disease |
|
| ir Unknown |
|
|
|
| Participants with SAEs Treatment-Related |
|
| Deaths |
|
| Deaths Treatment-Related |
|
| Participants discontinued due to AE(s) |
|
| Nominal Ipilimumab Induction Dose Number 2 |
|
| Nominal Ipilimumab Induction Dose Number 3 |
|
| Nominal Ipilimumab Induction Dose Number 4 |
|
| End of Ipilimumab Induction dosing Period |
|
| null hypothesis that the pattern of mean ALC values over time is the same in all treatment groups. Test of overall time-by-treatment interaction used an omnibus conditional F-test. | Omnibus conditional F-test | 10 Degrees Freedom (DF) in numerator and 335 DF in denominator. | 0.5 | P-values were not corrected for multiple testing. F Statistic =0.94 | No | Superiority or Other |
| null hypothesis that the pattern of mean ALC values over time is the same in the given pair of treatment groups. | conditional F-test | 5 Degrees Freedom (DF) in numerator and 335 DF in denominator. | 0.37 | P-values were not corrected for multiple testing. F Statistic =1.08 | No | Superiority or Other |
| null hypothesis that the pattern of mean ALC values over time is the same in the given pair of treatment groups. | conditional F-test | 5 Degrees Freedom (DF) in numerator and 335 DF in denominator. | 0.85 | P-values were not corrected for multiple testing. F Statistic =0.39 | No | Superiority or Other |
| null hypothesis that the pattern of mean ALC values over time is the same in the given pair of treatment groups. | conditional F-test | 5 Degrees Freedom (DF) in numerator and 335 DF in denominator. | 0.22 | P-values were not corrected for multiple testing. F Statistic = 1.41 | No | Superiority or Other |
| Diastolic Blood Pressure at Week 48 (N=1, 4, 4) |
|
| Systolic Blood Pressure at Week 16 (N=1, 6, 9) |
|
| Systolic Blood Pressure at Week 48 (N=1, 4, 4) |
|
| Pulse Rate at Week 48 (N=1, 4, 4) |
|
| Respiration Rate at Week 48 (N=1, 3, 3) |
|
| Temperature at Week 48 (N=1, 4, 4) |
|
| Title | Measurements |
|---|---|
|
| Hemoglobin Grade 2 |
|
| Hemoglobin Grade 3 |
|
| Hemoglobin Not Reported |
|
| Title | Measurements |
|---|---|
|
| Leukocytes Grade 2 |
|
| Leukocytes Grade 3 |
|
| Leukocytes Grade 4 |
|
| Leukocytes Not Reported |
|
| Title | Measurements |
|---|---|
|
| Lymphocytes Grade 2 |
|
| Lymphocytes Grade 3 |
|
|
| Neutrophils Grade 3 |
|
|
| Neutrophils Plus Bands Grade 3 |
|
|
| Title | Measurements |
|---|---|
|
| ALT Grade 2 |
|
| Title | Measurements |
|---|---|
|
| AST Grade 2 |
|
| Title | Measurements |
|---|---|
|
|
| Alkaline Phosphatase Grade 2 |
|
|
| Total Bilirubin Grade 2 |
|
|
| Serum Potassium (High) Grade 2 |
|
|
| Total Amylase Grade 2 |
|
| Total Amylase Grade 3 |
|
|
|
| Total Lipase Grade 4 |
|
| Total Lipase Not Reported |
|
| Title | Measurements |
|---|---|
|