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This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of rhuMab 2C4 (Perjeta) and docetaxel (Taxotere) in participants with advanced solid tumors that have progressed during or after standard therapy, or for which no standard therapy is available. Participants will be enrolled and evaluated for dose-limiting toxicities (DLTs) in escalating-dose cohorts in order to determine the maximum tolerated dose (MTD).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RhuMab 2C4 + Docetaxel 100 mg/m^2 (Level 3) | Experimental | Docetaxel will be administered via intravenous (IV) infusion on Day 1 of each 3-week cycle at a dose of 100 mg/m^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment. |
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| RhuMab 2C4 + Docetaxel 60 mg/m^2 (Level 1) | Experimental | Docetaxel will be administered via IV infusion on Day 1 of each 3-week cycle at a dose of 60 mg/m^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment. |
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| RhuMab 2C4 + Docetaxel 75 mg/m^2 (Level 2) | Experimental | Docetaxel will be administered via IV infusion on Day 1 of each 3-week cycle at a dose of 75 mg/m^2 per day, and rhuMab 2C4 will be given on Day 1 of each 3-week cycle as a fixed-dose 420-mg IV infusion. For Cycle 1 only, rhuMab 2C4 administration will be delayed to Day 2 with an initial 840-mg loading dose. The incidence of DLTs will be used to guide intrapatient dose modification, as well as subsequent enrollment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Docetaxel | Drug | Participants will receive docetaxel on Day 1 of each 3-week cycle as 60, 75, or 100 mg/m^2 via IV infusion. Treatment may continue until disease progression, unacceptable toxicity, or consent withdrawal. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab | A prior dose level was defined as an MTD if at a certain dose level, there were greater than or equal to (≥) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs). If there were no DLTs or DLTs were seen in less than (<) 2 participants in the highest dose level, that was considered as MTD. Participants received escalating doses of docetaxel and pertuzumab until DLTs were observed. DLTs were defined as any of the following: 1) Any non-hematological toxicity ≥ Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. | Cycle 1 Up to Day 15 |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel | The biological half-life or terminal half-life of pertuzumab is the time in days it takes for it to lose half of its pharmacologic activity. | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rotterdam | 3075 EA | Netherlands | ||||
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| ID | Title | Description |
|---|---|---|
| FG000 | Docetaxel 60 Plus (+) Pertuzumab 1050 | Participants received 60 milligrams per square meter (mg/m^2) docetaxel and 1050 mg of pertuzumab as an intravenous (IV) infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 hours (h) apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. |
| FG001 | Docetaxel 75 + Pertuzumab 1050 | Participants received 75 mg/m^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. |
| FG002 | Docetaxel 75 + Pertuzumab 420 | Participants received 75 mg/m^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. |
| FG003 | Docetaxel 100 + Pertuzumab 420 | Participants received 100 mg/m^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1: First 6 Cycles |
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| ||||||||||||||||||
| Period 2: Extension Phase |
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The Intent-To-Treat (ITT) Population included all participants who received any amount of the study medication.
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| ID | Title | Description |
|---|---|---|
| BG000 | Docetaxel 60 Plus (+) Pertuzumab 1050 | Participants received 60 mg/m^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab | A prior dose level was defined as an MTD if at a certain dose level, there were greater than or equal to (≥) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs). If there were no DLTs or DLTs were seen in less than (<) 2 participants in the highest dose level, that was considered as MTD. Participants received escalating doses of docetaxel and pertuzumab until DLTs were observed. DLTs were defined as any of the following: 1) Any non-hematological toxicity ≥ Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. | Safety Population: included all participants who received any amount of study medication and who had at least one post-baseline safety follow-up. | Posted | Number | mg/m^2 | Cycle 1 Up to Day 15 |
Adverse events were continuously monitored from Screening until 4 weeks after the final visit.
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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 | Docetaxel 60 Plus (+) Pertuzumab 1050 | Participants received 60 mg/m^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-La Roche | 800-821-8590 | genentech@druginfo.com |
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| ID | Term |
|---|---|
| D000077143 | Docetaxel |
| C485206 | pertuzumab |
| ID | Term |
|---|---|
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
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|
| RhuMab 2C4 | Drug | Participants will receive rhuMab 2C4 on Day 1 of each 3-week cycle as 420 mg via IV infusion. For Cycle 1 ony, rhuMab will be administered on Day 2, at least 24 hours after docetaxel and following an initial 840-mg loading dose. Treatment may continue until disease progression, unacceptable toxicity, or consent withdrawal. |
|
|
| Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel | Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as micrograms per milliliter (μg/mL). | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
| Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel | The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-last is calculated from time 0 (prior to administration of medication) to last measured data point. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as micrograms times days per milliliter (μg*day/mL). | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
| AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel | The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as μg*day/mL. | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
| Clearance (Cl) of Pertuzimab in Combination With Docetaxel | Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per day (mL/day). | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
| Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel | The volume of distribution at steady state (Vz), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
| Mean Residence Time (MRT) of Pertuzumab | MRT is the average time that pertuzumab is present in the systemic circulation and is measured in days. | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
| Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Best Overall response was evaluated as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). CR: complete disappearance of all target lesions. PR: at least a 30 percent (%) decrease in the sum of the longest diameters. SD: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameters since the treatment started. PD: at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters of the target lesions recorded since the treatment started, including screening, or the appearance of one or more new lesions. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit. | Weeks 7 (Cycle 2),13 (Cycle 4) and Final Visit Up to 22 weeks |
| Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Ejection fraction (EF) is the fraction of outbound blood pumped from the heart with each heartbeat. It is commonly measured by echocardiogram and serves as a general measure of a person's cardiac function. Changes in LVEF were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria. The decrease in LVEF has been categorized as follows: A) Increase, no change, decrease from baseline less than (<) 10%; B) Absolute value <50% and decrease from baseline greater than or equal to (≥) 10%; C) Absolute value <50% and decrease from baseline≥15% ; D) Other. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit. | Baseline, Weeks 7(Cycle 2), 13 (Cycle 4) and Final Visit Up to Week 22 |
| t1/2 for Docetaxel Alone and in Combination With Pertuzumab | The biological half-life or terminal half-life of docetaxel is the time in hours it takes for it to lose half of its pharmacologic activity. Data for "docetaxel alone" arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose |
| Tmax for Docetaxel Alone and in Combination With Pertuzumab | Tmax is defined as the time after administration of a drug when the maximum plasma concentration is reached; Data for "docetaxel alone" arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. When the rate of absorption equals the rate of elimination. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose |
| Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as nanograms per milliliter (ng/mL). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose |
| AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as ng*h/mL. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose |
| Vss for Docetaxel Alone and in Combination With Pertuzumab | The volume of distribution at steady state (Vss), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose |
| CL for Docetaxel Alone and in Combination With Pertuzumab | Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per hour per meter squared (mL/h/m^2). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose |
| Number of Participants With DLTs | DLTs were defined as any of the following: 1) Any non-hematological toxicity greter than or equal to (≥) Grade 3 according t0 CTCAE version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. | From Baseline until 4 weeks after the end of treatment |
| Sutton |
| SM2 5PT |
| United Kingdom |
| Insufficient Therapeutic Response |
|
| Refused Treatment |
|
| Completed 6 Cycles of Therapy |
|
| COMPLETED |
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| NOT COMPLETED |
|
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| BG001 | Docetaxel 75 + Pertuzumab 1050 | Participants received 75 mg/m^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. |
| BG002 | Docetaxel 75 + Pertuzumab 420 | Participants received 75 mg/m^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. |
| BG003 | Docetaxel 100 + Pertuzumab 420 | Participants received 100 mg/m^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. |
| BG004 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| ID |
|---|
| Title |
|---|
| Description |
|---|
| OG000 | Entire Study Population | Participants received escalating dose levels of combination of docetaxel and pertuzumab. Participants received docetaxel 60 mg/m^2 and pertuzumab 1050 mg at dose level 1, docetaxel 75 mg/m^2 and pertuzumab 1050 mg at dose level 2, docetaxel 75 mg/m^2 and pertuzumab 420 mg at dose level 3 or 100 mg/m^2 and pertuzumab 420 mg at dose level 4 until DLTs were observed. |
|
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| Secondary | Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel | The biological half-life or terminal half-life of pertuzumab is the time in days it takes for it to lose half of its pharmacologic activity. | ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. number (n) equals (=) number of participants analyzed at the specified timepoint for each arm, respectively. | Posted | Median | Full Range | days | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
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| Secondary | Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel | Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as micrograms per milliliter (μg/mL). | ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively. | Posted | Mean | Standard Deviation | μg/mL | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
|
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| Secondary | Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel | The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-last is calculated from time 0 (prior to administration of medication) to last measured data point. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as micrograms times days per milliliter (μg*day/mL). | ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively. | Posted | Mean | Standard Deviation | μg*day/mL | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
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| Secondary | AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel | The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as μg*day/mL. | ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively. | Posted | Mean | Standard Deviation | μg*day/mL | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
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| Secondary | Clearance (Cl) of Pertuzimab in Combination With Docetaxel | Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per day (mL/day). | ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively. | Posted | Mean | Standard Deviation | mL/day | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
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| Secondary | Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel | The volume of distribution at steady state (Vz), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. | ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively. | Posted | Mean | Standard Deviation | mL | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
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| Secondary | Mean Residence Time (MRT) of Pertuzumab | MRT is the average time that pertuzumab is present in the systemic circulation and is measured in days. | ITT population; Participants in any cohort infused with the specified dose of pertuzumab were included in analysis. n = number of participants analyzed at the specified timepoint for each arm, respectively. | Posted | Mean | Standard Deviation | days | Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22 |
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| Secondary | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria | Best Overall response was evaluated as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). CR: complete disappearance of all target lesions. PR: at least a 30 percent (%) decrease in the sum of the longest diameters. SD: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameters since the treatment started. PD: at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters of the target lesions recorded since the treatment started, including screening, or the appearance of one or more new lesions. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit. | ITT population; n = number of participants still receiving treatment at the specified cycle for each arm respectively. | Posted | Number | percentage of participants | Weeks 7 (Cycle 2),13 (Cycle 4) and Final Visit Up to 22 weeks |
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| Secondary | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint | Ejection fraction (EF) is the fraction of outbound blood pumped from the heart with each heartbeat. It is commonly measured by echocardiogram and serves as a general measure of a person's cardiac function. Changes in LVEF were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria. The decrease in LVEF has been categorized as follows: A) Increase, no change, decrease from baseline less than (<) 10%; B) Absolute value <50% and decrease from baseline greater than or equal to (≥) 10%; C) Absolute value <50% and decrease from baseline≥15% ; D) Other. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit. | ITT population; n = number of participants still receiving treatment at the specified cycle for each arm, respectively. | Posted | Number | percentage of participants | Baseline, Weeks 7(Cycle 2), 13 (Cycle 4) and Final Visit Up to Week 22 |
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| Secondary | t1/2 for Docetaxel Alone and in Combination With Pertuzumab | The biological half-life or terminal half-life of docetaxel is the time in hours it takes for it to lose half of its pharmacologic activity. Data for "docetaxel alone" arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. | ITT population; Data from Cohort 2 (docetaxel 75 mg/m^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle. | Posted | Median | Full Range | days | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose |
|
|
|
| Secondary | Tmax for Docetaxel Alone and in Combination With Pertuzumab | Tmax is defined as the time after administration of a drug when the maximum plasma concentration is reached; Data for "docetaxel alone" arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. When the rate of absorption equals the rate of elimination. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. | ITT population; Data from Cohort 2 (docetaxel 75 mg/m^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle. | Posted | Median | Full Range | days | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose |
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| Secondary | Cmax for Docetaxel Alone and in Combination With Pertuzumab | Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as nanograms per milliliter (ng/mL). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. | ITT population; Data from Cohort 2 (docetaxel 75 mg/m^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle. | Posted | Mean | Standard Deviation | ng/mL | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose |
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| Secondary | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab | The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as ng*h/mL. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. | ITT population; Data from Cohort 2 (docetaxel 75 mg/m^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle. | Posted | Mean | Standard Deviation | ng*h/mL | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose |
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| Secondary | Vss for Docetaxel Alone and in Combination With Pertuzumab | The volume of distribution at steady state (Vss), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. | ITT population; Data from Cohort 2 (docetaxel 75 mg/m^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle. | Posted | Mean | Standard Deviation | mL/m^2 | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose |
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| Secondary | CL for Docetaxel Alone and in Combination With Pertuzumab | Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per hour per meter squared (mL/h/m^2). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. | ITT population; Data from Cohort 2 (docetaxel 75 mg/m^2 and pertuzumab 1050 mg) were excluded because there were only 2 participant data. It was planned not to report PK data, if less than or equal to 2 participants were analyzed. n= number of participants analyzed at the specified cycle. | Posted | Mean | Standard Deviation | mL/h/m^2 | Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose |
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| Secondary | Number of Participants With DLTs | DLTs were defined as any of the following: 1) Any non-hematological toxicity greter than or equal to (≥) Grade 3 according t0 CTCAE version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. | Safety Population | Posted | Number | number of participants | From Baseline until 4 weeks after the end of treatment |
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| 3 |
| 6 |
| 6 |
| 6 |
| EG001 | Docetaxel 75 + Pertuzumab 1050 | Participants received 75 mg/m^2 docetaxel and 1050 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. | 2 | 2 | 2 | 2 |
| EG002 | Docetaxel 75 + Pertuzumab 420 | Participants received 75 mg/m^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. | 0 | 6 | 6 | 6 |
| EG003 | Docetaxel 100 + Pertuzumab 420 | Participants received 100 mg/m^2 docetaxel and 420 mg of pertuzumab as an IV infusion every 3 weeks until disease progression, unacceptable toxicity, or consent withdrawal. In Cycle 1 participants received a loading dose of 840 mg of pertuzumab as an IV infusion. Further in Cycle 1 Docetaxel was administered on Day 1 and pertuzumab was administered at least 24 h apart on Day 2. Cycle 2 onwards pertuzumab was administered on Day 1 immediately followed by docetaxel. In addition all participants received 8 mg of dexamethasone or its equivalent as corticosteroid premedication. | 3 | 5 | 5 | 5 |
| Nausea | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA (7.1) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (7.1) | Non-systematic Assessment |
|
| Paralysis | Nervous system disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Mouth ulceration | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Proctalgia | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Abdominal discomfort | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Abdominal pain lower | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Anal fissure | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Ascites | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Gingivitis | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Glossitis | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Oesophagitis | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Proctitis | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Tongue ulceration | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Fatigue | General disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Mucosal inflammation | General disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Malaise | General disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Chest pain | General disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Chills | General disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Extravasation | General disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Pyrexia | General disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Injection site haemorrhage | General disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Pain | General disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Suprapubic pain | General disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Dysgeusia | Nervous system disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Paraesthesia | Nervous system disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Ageusia | Nervous system disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Hypoaesthesia | Nervous system disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Neuropathy | Nervous system disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Neuropathy peripheral | Nervous system disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Syncope | Nervous system disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Dry skin | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Erythema multiforme | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Periorbital oedema | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Rash follicular | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Lower respiratory tract infection | Infections and infestations | MedDRA (7.1) | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA (7.1) | Non-systematic Assessment |
|
| Oral candidiasis | Infections and infestations | MedDRA (7.1) | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA (7.1) | Non-systematic Assessment |
|
| Candidiasis | Infections and infestations | MedDRA (7.1) | Non-systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA (7.1) | Non-systematic Assessment |
|
| Eye infection | Infections and infestations | MedDRA (7.1) | Non-systematic Assessment |
|
| Localised infection | Infections and infestations | MedDRA (7.1) | Non-systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA (7.1) | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA (7.1) | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Pharyngolaryngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Throat irritation | Respiratory, thoracic and mediastinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Nasal mucosal disorder | Respiratory, thoracic and mediastinal disorders | MedDRA (7.1) | Non-systematic Assessment |
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| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Chest wall pain | Musculoskeletal and connective tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Limb discomfort | Musculoskeletal and connective tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Shoulder pain | Musculoskeletal and connective tissue disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Confusional state | Psychiatric disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Flushing | Vascular disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Lymphoedema | Vascular disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Phlebitis | Vascular disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Lacrimation | Eye disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Diplopia | Eye disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Dry eye | Eye disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Visual acuity reduced | Eye disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Anaemia | Blood and lymphatic system disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Lymph node pain | Blood and lymphatic system disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA (7.1) | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA (7.1) | Non-systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Ventricular disfunction | Cardiac disorders | MedDRA (7.1) | Non-systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA (7.1) | Non-systematic Assessment |
|
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (7.1) | Non-systematic Assessment |
|
| Gential Haemorrhage | Reproductive system and breast disorders | MedDRA (7.1) | Non-systematic Assessment |
|
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| Cycle 2 (n=7,0,10) |
|
| Cycle 2 (n=7,0,10) |
|
| Cycle 2 (n=7,0,10) |
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| Cycle 2 (n=7,0,10) |
|
| Cycle 2 (n=7,0,10) |
|
| Cycle 2 (n=7,0,10) |
|
| Cycle 2 (n=7,0,10) |
|
| Cycle 2:PR (n=6,1,6,4) |
|
| Cycle 2:SD (n=6,1,6,4) |
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| Cycle 2:PD (n=6,1,6,4) |
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| Cycle 2:Missing (n=6,1,6,4) |
|
| Cycle 4:CR (n=5,1,5,3) |
|
| Cycle 4:PR (n=5,1,5,3) |
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| Cycle 4:SD (n=5,1,5,3) |
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| Cycle 4:PD (n=5,1,5,3) |
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| Cycle 4:Missing (n=5,1,5,3) |
|
| Final visit:CR (n=6,2,6,5) |
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| Final visit:PR (n=6,2,6,5) |
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| Final visit:SD (n=6,2,6,5) |
|
| Final visit:PD (n=6,2,6,5) |
|
| Final visit:Missing (n=6,2,6,5) |
|
| Cycle 2: B (n=6,1,6,4) |
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| Cycle 2: C (n=6,1,6,4) |
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| Cycle 2: D (n=6,1,6,4) |
|
| Cycle 4: A (n=5,1,4,3) |
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| Cycle 4: B (n=5,1,4,3) |
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| Cycle 4: C (n=5,1,4,3) |
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| Cycle 4: D (n=5,1,4,3) |
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| Final Visit: A (n=3,1,5,2) |
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| Final Visit: B (n=3,1,5,2) |
|
| Final Visit: C (n=3,1,5,2) |
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| Final Visit: D (n=3,1,5,2) |
|
| Cycle 2(n=0,6,0,6,0,4) |
|
| Cycle 2 (n=0,6,0,6,0,4) |
|
| Cycle 2 (n=0,6,0,6,0,4) |
|
| Cycle 2 (n=0,6,0,6,0,4) |
|
| Cycle 2 (n=0,6,0,6,0,4) |
|
| Cycle 2 (n=0,6,0,6,0,4) |
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