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This open-label, non-randomized study will assess the mass balance, metabolism, routes and rates of elimination as well as efficacy and safety of RO5185426 (RG7204; PLEXXIKON; PLX4032) in previously treated or untreated patients with metastatic melanoma. Patients will receive continuous twice daily oral treatment with RO5185426. On Day 15, a 14C-labeled dose will be administered. Anticipated time on study treatment is until disease progression occurs.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Arm | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RO5185426 | Drug | Continuous oral dosing b.i.d. , on Day 15 a C isotope labeled dose will be administered |
|
| Measure | Description | Time Frame |
|---|---|---|
| Plasma RO5185426 Trough Concentrations on Days 15,16, and 17 | Pre-dose on Days 15, 16 and 17 | |
| Maximum Plasma Concentration of 14C-labeled RO5185426 (Cmax) in Both Blood and Plasma | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). 14C-labeled RO5185426 given was equivalent to ≤1 millisieverts (mSv). | 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours) |
| Time to Reach Cmax in Both Blood and Plasma | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). | 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours) |
| Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUClast) of 14C-RO5185426 in Both Blood and Plasma | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). 14C-labeled RO5185426 given was equivalent to ≤1mSv. | 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours) |
| Half-life of 14C-labeled RO5185426 in Both Blood and Plasma |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With a Response by Confirmed Best Overall Response | Best overall response (according to Response Evaluation Criteria In Solid Tumors 1.1 criteria) was defined as best response recorded from start of treatment until disease progression which included complete response (CR) or partial response (PR) that had been confirmed by second tumor assessment no less than (<) 4 weeks after criteria for response were first met. Confirmed CR: disappearance of all target and non-target lesions; no new lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 millimeters (mm). Confirmed PR: at least 30% decrease in sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Disease progression: at least 20% increase in sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. |
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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 |
|---|---|---|---|---|---|---|
| Zurich | 8091 | Switzerland |
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| ID | Title | Description |
|---|---|---|
| FG000 | 14C-labeled RO5185426 | Participants received non-labeled RO5185426 film-coated tablets 960 milligrams (mg) orally two times daily (BID) from Day 1 to Day 14. On Day 15, participants received a single dose of 960 mg RO5185426 with a maximum of 2.56 millibecquerel (69.2 microcurie) of 14C RO5185426. After Day 15, participants received non-labeled RO5185426 film-coated tablets 960 mg orally BID until the development of progressive disease, unacceptable toxicity, consent withdrawal, death, lost to follow-up or any other criteria for removal as determined by the investigator. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All enrolled participants were analyzed.
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| ID | Title | Description |
|---|---|---|
| BG000 | 14C-labeled RO5185426 | Participants received non-labeled RO5185426 film-coated tablets 960 mg orally BID from Day 1 to Day 14. On Day 15, participants received a single dose of 960 mg RO5185426 with a maximum of 2.56 millibecquerel (69.2 microcurie) of 14C RO5185426. After Day 15, participants received non-labeled RO5185426 film-coated tablets 960 mg orally BID until the development of progressive disease, unacceptable toxicity, consent withdrawal, death, lost to follow-up or any other criteria for removal as determined by the investigator. |
| 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 | Plasma RO5185426 Trough Concentrations on Days 15,16, and 17 | Pharmacokinetic (PK) Analysis Population: participants from whom the level of radioactivity recovered from excreta (urine and feces) was ≤ 1% of the radioactivity in the administered dose between any two successive 48-hour interval assessments. | Posted | Mean | Standard Deviation | micrograms per milliliter | Pre-dose on Days 15, 16 and 17 |
|
Baseline up to 28 days after last dose (up to 869 days)
Safety population included all participants who received at least 1 dose of study drug.
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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 | 14C-labeled RO5185426 | Participants received non-labeled RO5185426 film-coated tablets 960 mg orally BID from Day 1 to Day 14. On Day 15, participants received a single dose of 960 mg RO5185426 with a maximum of 2.56 millibecquerel (69.2 microcurie) of 14C RO5185426. After Day 15, participants received non-labeled RO5185426 film-coated tablets 960 mg orally BID until the development of progressive disease, unacceptable toxicity, consent withdrawal, death, lost to follow-up or any other criteria for removal as determined by the investigator. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Keratoacanthoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Communications | Hoffmann-LaRoche | 800 821-8590 | genentech@druginfo.com |
Not provided
| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). |
| 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours) |
| AUC Ratio of Blood:Plasma 14C-labeled RO5185426 | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). | 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours) |
| 14C-labeled RO5185426 Recovery: Percentage of Dose Excreted in Feces and Urine | Urinary and fecal samples were analyze for the percentage dose recovered as total radioactivity. The radioactivity was determined on a Packard liquid scintillation counter. Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). | Urine:0 hour (pre dose),in quantitative fraction(0-6,6-12,12-24 hours) post dose on Day 15,during 24 hour interval thereafter;Feces:From Day 14 upto pre dose on Day 15,during 24 hour interval post dose until recovery criterion;(maximum:432 hours for both) |
| Percentage of Total Integrated Radioactivity in Plasma of 14C-labeled RO5185426 and 14C-labeled Metabolite | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Plasma samples were pooled over three time intervals for this analysis based on available radioactive counts (4 + 6 hours, 12 + 24 hours, and 36 + 48 hours). Radioactivity was measured in terms of region of interest by high performance liquid chromatography. The radiolabelled components in each chromatogram were evaluated to determine retention times and peak area values. Data for 14C-labeled RO5185426 and 14C-labeled metabolite (mono-hydroxy) are reported. | 4+6 hours, 12 +24 hours, 36+48 hours post dose on Day 15 |
| Plasma 14C-labeled RO5185426 and 14C-labeled Metabolite Levels | Collection of samples for radioactivity continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48 hour interval assessments). Plasma samples were pooled over three time intervals for this analysis based on available radioactive counts (4 + 6 hours, 12 + 24 hours, and 36 + 48 hours). The concentrations were measured in nanogram equivalent per gram which was calculated based on ratio of dosed radioactivity and the last dose of RO5185426. The concentration values represented the drug portion of the last dose. Data for 14C-labeled RO5185426 and 14C-labeled metabolite (mono-hydroxy) are reported. | 4+6 hours, 12 +24 hours, 36+48 hours post dose on Day 15 |
| Percentage of Total Integrated Radioactivity in Feces of 14C-labeled RO5185426 and 14C-labeled Metabolite | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Fecal samples were pooled over two time intervals for this analysis (0-24 + 24-48 hours, 48-72 + 72-96 hours). Radioactivity was measured in terms of region of interest by high performance liquid chromatography. The radiolabelled components in each chromatogram were evaluated to determine retention times and peak area values. Data for 14C-labeled RO5185426 and 14C-labeled metabolites (glucosylation, mono-hydroxy, and glucuronide) are reported. | 0-24 + 24-48 hours, 48-72 + 72-96 hours post dose on Day 15 |
| Percentage of Total Dose in 14C-labeled RO5185426 and 14C-labeled Metabolite in Pooled Fecal Samples | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Fecal samples were pooled over 2 time intervals (0-24 + 24-48 hours, 48-72 + 72-96 hours) for measurement of 14C-labeled RO5185426 and 14C-labeled metabolites (glucosylation, mono-hydroxy, glucuronide) levels. | 0-24 + 24-48 hours, 48-72 + 72-96 hours post dose on Day 15 |
| Percentage of Total Integrated Radioactivity in Urine of 14C-labeled RO5185426 and 14C-labeled Metabolite | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Urine samples were pooled over period of 96 hours (pool of 0-6 + 6-12 + 12-24 + 24-48 + 48-72 + 72-96 hour samples), Radioactivity was measured in terms of region of interest by high performance liquid chromatography. The radiolabelled components in each chromatogram were evaluated to determine retention times and peak area values. Data for 14C-labeled RO5185426 and 14C-labeled metabolites (2 unknown metabolites, glucosylation, mono-hydroxy) are reported. | 0 up to 96 hours post dose on Day 15 |
| Percentage of Total Dose in 14C-labeled RO5185426 and 14C-labeled Metabolite in Pooled Urine Samples | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Urine samples were pooled over period of 96 hours (pool of 0-6 + 6-12 + 12-24 + 24-48 + 48-72 + 72-96 hour samples). Data for parent drug (RO5185426) and metabolites (2 unknown metabolites, glucosylation, mono-hydroxy) are reported. | 0 up to 96 hours post dose on Day 15 |
| From Baseline then Day 1 of Cycle 3 thereafter, Day 1 of every other cycle (every 2 months) until disease progression, withdrawal from study or death (maximum 841 days) |
| Overall Survival | Overall survival was defined as the time from the date of first treatment to the date of death, regardless of the cause of death. | From Baseline then Day 1 of Cycle 3 thereafter, Day 1 of every other cycle (every 2 months) until death (maximum 841 days) |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
|
|
| Secondary | Number of Participants With a Response by Confirmed Best Overall Response | Best overall response (according to Response Evaluation Criteria In Solid Tumors 1.1 criteria) was defined as best response recorded from start of treatment until disease progression which included complete response (CR) or partial response (PR) that had been confirmed by second tumor assessment no less than (<) 4 weeks after criteria for response were first met. Confirmed CR: disappearance of all target and non-target lesions; no new lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 millimeters (mm). Confirmed PR: at least 30% decrease in sum of diameters of target lesions (taking as reference the baseline sum diameters), no progression in non-target lesions, and no new lesions. Disease progression: at least 20% increase in sum of diameters of target lesions compared to smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. | Safety population included all participants who received at least 1 dose of study drug. | Posted | Number | participants | From Baseline then Day 1 of Cycle 3 thereafter, Day 1 of every other cycle (every 2 months) until disease progression, withdrawal from study or death (maximum 841 days) |
|
|
|
| Secondary | Overall Survival | Overall survival was defined as the time from the date of first treatment to the date of death, regardless of the cause of death. | The data was not collected, as planned, due to small number of participants enrolled in the study. | Posted | From Baseline then Day 1 of Cycle 3 thereafter, Day 1 of every other cycle (every 2 months) until death (maximum 841 days) |
|
|
| Primary | Maximum Plasma Concentration of 14C-labeled RO5185426 (Cmax) in Both Blood and Plasma | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). 14C-labeled RO5185426 given was equivalent to ≤1 millisieverts (mSv). | PK Analysis Population. Number of participants analyzed = participants with measurable data for this outcome. | Posted | Mean | Standard Deviation | micrograms equivalent per milliliter | 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours) |
|
|
|
| Primary | Time to Reach Cmax in Both Blood and Plasma | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). | PK Analysis Population. Number of participants analyzed = participants with measurable data for this outcome. | Posted | Median | Full Range | hours | 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours) |
|
|
|
| Primary | Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Sample (AUClast) of 14C-RO5185426 in Both Blood and Plasma | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). 14C-labeled RO5185426 given was equivalent to ≤1mSv. | PK Analysis Population. Number of participants analyzed = participants with measurable data for this outcome. | Posted | Mean | Standard Deviation | (micrograms equivalent/milliliter)*hour | 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours) |
|
|
|
| Primary | Half-life of 14C-labeled RO5185426 in Both Blood and Plasma | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). | PK Analysis Population. Number of participants analyzed = participants with measurable data for this outcome. | Posted | Mean | Standard Deviation | hour | 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours) |
|
|
|
| Primary | AUC Ratio of Blood:Plasma 14C-labeled RO5185426 | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). | PK Analysis Population. Number of participants analysed = participants with measurable data for this outcome. | Posted | Mean | Standard Deviation | ratio | 0 hour (prior to evening dose) on Day 14; 0 hour (pre dose), 1, 2, 4, 6, 12, 24, 36, 48, 72, 96, 168, 216, 312 hours post dose on Day 15, and then every 96 hour until recovery criteria met (maximum: 432 hours) |
|
|
|
| Primary | 14C-labeled RO5185426 Recovery: Percentage of Dose Excreted in Feces and Urine | Urinary and fecal samples were analyze for the percentage dose recovered as total radioactivity. The radioactivity was determined on a Packard liquid scintillation counter. Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). | PK Analysis Population. One participant was excluded in the analysis because of contamination of urine sample with feces. | Posted | Mean | Standard Deviation | percentage of dose recovered | Urine:0 hour (pre dose),in quantitative fraction(0-6,6-12,12-24 hours) post dose on Day 15,during 24 hour interval thereafter;Feces:From Day 14 upto pre dose on Day 15,during 24 hour interval post dose until recovery criterion;(maximum:432 hours for both) |
|
|
|
| Primary | Percentage of Total Integrated Radioactivity in Plasma of 14C-labeled RO5185426 and 14C-labeled Metabolite | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Plasma samples were pooled over three time intervals for this analysis based on available radioactive counts (4 + 6 hours, 12 + 24 hours, and 36 + 48 hours). Radioactivity was measured in terms of region of interest by high performance liquid chromatography. The radiolabelled components in each chromatogram were evaluated to determine retention times and peak area values. Data for 14C-labeled RO5185426 and 14C-labeled metabolite (mono-hydroxy) are reported. | PK Analysis Population. | Posted | Mean | Standard Deviation | percentage of total radioactivity | 4+6 hours, 12 +24 hours, 36+48 hours post dose on Day 15 |
|
|
|
| Primary | Plasma 14C-labeled RO5185426 and 14C-labeled Metabolite Levels | Collection of samples for radioactivity continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48 hour interval assessments). Plasma samples were pooled over three time intervals for this analysis based on available radioactive counts (4 + 6 hours, 12 + 24 hours, and 36 + 48 hours). The concentrations were measured in nanogram equivalent per gram which was calculated based on ratio of dosed radioactivity and the last dose of RO5185426. The concentration values represented the drug portion of the last dose. Data for 14C-labeled RO5185426 and 14C-labeled metabolite (mono-hydroxy) are reported. | PK Analysis Population. | Posted | Mean | Standard Deviation | nanogram equivalent per gram | 4+6 hours, 12 +24 hours, 36+48 hours post dose on Day 15 |
|
|
|
| Primary | Percentage of Total Integrated Radioactivity in Feces of 14C-labeled RO5185426 and 14C-labeled Metabolite | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Fecal samples were pooled over two time intervals for this analysis (0-24 + 24-48 hours, 48-72 + 72-96 hours). Radioactivity was measured in terms of region of interest by high performance liquid chromatography. The radiolabelled components in each chromatogram were evaluated to determine retention times and peak area values. Data for 14C-labeled RO5185426 and 14C-labeled metabolites (glucosylation, mono-hydroxy, and glucuronide) are reported. | PK Analysis Population. | Posted | Mean | Standard Deviation | percentage of total radioactivity | 0-24 + 24-48 hours, 48-72 + 72-96 hours post dose on Day 15 |
|
|
|
| Primary | Percentage of Total Dose in 14C-labeled RO5185426 and 14C-labeled Metabolite in Pooled Fecal Samples | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Fecal samples were pooled over 2 time intervals (0-24 + 24-48 hours, 48-72 + 72-96 hours) for measurement of 14C-labeled RO5185426 and 14C-labeled metabolites (glucosylation, mono-hydroxy, glucuronide) levels. | PK Analysis Population. | Posted | Mean | Standard Deviation | percentage of total dose administered | 0-24 + 24-48 hours, 48-72 + 72-96 hours post dose on Day 15 |
|
|
|
| Primary | Percentage of Total Integrated Radioactivity in Urine of 14C-labeled RO5185426 and 14C-labeled Metabolite | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Urine samples were pooled over period of 96 hours (pool of 0-6 + 6-12 + 12-24 + 24-48 + 48-72 + 72-96 hour samples), Radioactivity was measured in terms of region of interest by high performance liquid chromatography. The radiolabelled components in each chromatogram were evaluated to determine retention times and peak area values. Data for 14C-labeled RO5185426 and 14C-labeled metabolites (2 unknown metabolites, glucosylation, mono-hydroxy) are reported. | PK Analysis Population. | Posted | Mean | Standard Deviation | percentage of total radioactivity | 0 up to 96 hours post dose on Day 15 |
|
|
|
| Primary | Percentage of Total Dose in 14C-labeled RO5185426 and 14C-labeled Metabolite in Pooled Urine Samples | Collection of samples continued until the recovery criterion was met (radioactivity recovered from urine and feces ≤ 1 % of the radioactivity in the administered dose between any two successive 48-hour interval assessments). Urine samples were pooled over period of 96 hours (pool of 0-6 + 6-12 + 12-24 + 24-48 + 48-72 + 72-96 hour samples). Data for parent drug (RO5185426) and metabolites (2 unknown metabolites, glucosylation, mono-hydroxy) are reported. | PK Analysis Population. | Posted | Mean | Standard Deviation | percentage of total dose administered | 0 up to 96 hours post dose on Day 15 |
|
|
|
| 1 |
| 7 |
| 3 |
| 7 |
| 7 |
| 7 |
| Malignant Melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Non-systematic Assessment |
|
| Squamous Cell Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Non-systematic Assessment |
|
| Squamous Cell Carcinoma of Skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Non-systematic Assessment |
|
| Conjunctivital Hyperaemia | Eye disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Abdominal Distension | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Abdominal Pain | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Dry Mouth | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Gastrooesophageal Reflux Disease | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Lip Swelling | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Parotid Gland Enlargement | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Tongue Coated | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Oedema Peripheral | General disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Device Related Infection | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
|
| Erythema Induratum | Infections and infestations | MedDRA (16.0) | Non-systematic Assessment |
|
| Sunburn | Injury, poisoning and procedural complications | MedDRA (16.0) | Non-systematic Assessment |
|
| Thermal Burn | Injury, poisoning and procedural complications | MedDRA (16.0) | Non-systematic Assessment |
|
| Alanine Aminotransferase Increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
|
| Blood Potassium Decreased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
|
| Gamma-Glutamyltransferase Increased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
|
| Weight Decreased | Investigations | MedDRA (16.0) | Non-systematic Assessment |
|
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Joint Swelling | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Muscular Weakness | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Sensation of Heaviness | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Papilloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (16.0) | Non-systematic Assessment |
|
| Burning sensation | Nervous system disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Restlessness | Psychiatric disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Oropharyngeal Pain | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Rhinitis Allergic | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Dermatitis Atopic | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Hyperkeratosis | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Onychoclasis | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Papule | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Photosensitivity Reaction | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Pruritus Generalised | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Rash Follicular | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Rash Generalised | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Rash Macular | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Rash Maculo-Papular | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Seborrhoeic Dermatitis | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Skin Exfoliation | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Skin Induration | Skin and subcutaneous tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA (16.0) | 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.
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
|
| Title | Measurements |
|---|---|
|
| Mono-hydroxy Metabolite: 4 + 6 hours |
|
| Mono-hydroxy Metabolite: 12 + 24 hours |
|
| Mono-hydroxy Metabolite: 36 + 48 hours |
|
| Title | Measurements |
|---|---|
|
| Mono-hydroxy Metabolite: 4 + 6 hours |
|
| Mono-hydroxy Metabolite: 12 + 24 hours |
|
| Mono-hydroxy Metabolite: 36 + 48 hours |
|
|
| Glucosylation: 48-72 + 72-96 hours |
|
| Mono-hydroxy: 0-24 + 24-48 hours |
|
| Mono-hydroxy: 48-72 + 72-96 hours |
|
| Glucuronide: 0-24 + 24-48 hours |
|
| Glucuronide: 48-72 + 72-96 hours |
|
|
| Glucosylation: 48-72 + 72-96 hours |
|
| Mono-hydroxy: 0-24 + 24-48 hours |
|
| Mono-hydroxy: 48-72 + 72-96 hours |
|
| Glucuronide: 0-24 + 24-48 hours |
|
| Glucuronide: 48-72 + 72-96 hours |
|
| Title | Measurements |
|---|---|
|
| Glucosylation |
|
| Mono-hydroxy |
|
| Title | Measurements |
|---|---|
|
| Glucosylation |
|
| Mono-hydroxy |
|