Study Evaluating Biomarkers In Relapsed/Refractory Pediatric Solid Tumors

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00106353
• Collaborator: (none)
• Enrollment: 71
• Locations: 30
• Arm: 1
• Duration (Months): 82
• Patients Per Site: 2.4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This is an open label, two-part study of temsirolimus given as a 60-minute intravenous (IV) infusion once weekly to pediatric subjects with advanced solid tumors.

Part 1 is an ascending-dose study to evaluate the safety of IV temsirolimus given once weekly to subjects ages 1 to 21 years with advanced solid tumors disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available. (enrollment completed) Part 2 will be conducted in three groups of children with refractory or relapsed pediatric solid tumors. Subjects with the following tumor types will be enrolled: neuroblastoma, rhabdomyosarcoma, and high-grade gliomas. Subjects will receive IV temsirolimus once weekly until disease progression or unacceptable toxicity. (recruiting)

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma; Neoplasms	Drug: Torisel	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Safety and Exploratory Pharmacogenomic/Pharmacodynamic Study of Intravenous Temsirolimus (CCI-779) in Pediatric Subjects With Relapsed/Refractory Solid Tumors
• Study Start Date: Mar 1, 2005
• Actual Primary Completion Date: Oct 1, 2009
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 1.0

Drug: Torisel; 60-minute intravenous (IV) infusion once weekly to pediatric subjects with advanced solid tumors. Part 1 is an ascending-dose study to evaluate the safety of IV temsirolimus given once weekly to subjects ages 1 to 21 years with advanced solid tumors disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available. (enrollment completed) Part 2 will be conducted in three groups of children with refractory or relapsed pediatric solid tumors. Subjects with the following tumor types will be enrolled: neuroblastoma, rhabdomyosarcoma, and high-grade gliomas. Subjects will receive IV temsirolimus once weekly until disease progression or unacceptable toxicity.; Other Names: temsirolimus

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1 [Baseline up to End of Treatment (EOT) (within 30 days of last dose)]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

2. Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1 [Baseline up to EOT (within 30 days of last dose)]

   TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period.

3. Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1 [Baseline up to EOT (within 30 days of last dose)]

   TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period. National Cancer Institute (NCI)-graded Common Toxicity Criteria (CTC) provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death).

4. Number of Participants Who Died: Part 1 [Baseline up to EOT (within 30 days of last dose)]

   Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs).

5. Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1 [Baseline up to EOT (within 30 days of last dose)]

   SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability / incapacity or are a congenital anomaly or birth defect in the offspring of a study subject. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported.

6. Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1 [Baseline up to EOT (within 30 days of last dose)]

   Temporary interruption of study treatment; may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor.

7. Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1 [Baseline up to EOT (within 30 days of last dose)]

   Dose reduction for individual participant allowed if a dose limiting toxicity (DLT) occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of >3 weeks) unless investigator and medical monitor agree participant should remain in the study.

8. Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1 [Baseline up to EOT (within 30 days of last dose)]

   Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature >39 degrees Celsius (C), respiratory rate >20 beats per minute (bpm), and systolic and diastolic blood pressure (BP) >200/110 millimeters of mercury (mmHg). Participants may be reported in more than 1 category.

9. Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1 [Baseline up to EOT (within 30 days of last dose)]

   Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category.

10. Percentage of Participants With Objective Response (OR) at Week 12: Part 2 [Week 12]

    Measured as Complete response (CR), Very good partial response (VGPR), or Partial response (PR) on at least 2 occasions greater than or equal to (>=) 4 weeks apart within first 12 weeks. CR=disappearance of all primary and metastatic lesions; Homovanillic acid, Vanillymandelic acid (HVA/VMA) normal; bone marrow immunocytology negative. VGPR=disappearance of all metastatic lesions (residual areas of uptake on bone permitted); 90 to 99 percent (%) decrease in primary disease measurement; HVA/VMA normal or both decreased >90%. PR=at least 50% decrease in primary and metastatic disease. Number of bone sites decreased by at least 50%.

Secondary Outcome Measures

1. Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1 [Baseline up to Month 6]

   Maximum tolerated dose (MTD) defined as the dose level at which >=2 of 3 participants or >=2 of 6 participants if the dose level had been expanded, experienced a dose limiting toxicity (DLT) by day 21 after the first dose of study treatment. DLT defined as failure to recover to NCI-CTCAE version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of > 3 weeks) unless the investigator and the medical monitor agree that the subject should remain in the study.

2. Maximum Observed Plasma Concentration (Cmax): Part 1 [0 (pre-dose), 1, 2, 6, 24, and 168 hours (hrs) post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

3. Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1 [0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

4. Plasma Decay Half-Life (t1/2): Part 1 [0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

   Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

5. Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1 [0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

   AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).

6. Area Under the Concentration-Time Curve (AUC): Part 1 [0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

   AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

7. Clearance (CL): Part 1 [0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

   CL is a quantitative measure of the rate at which a drug substance is removed from the body.

8. Volume of Distribution at Steady State (Vss): Part 1 [0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

   Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.

9. Percentage of Participants With Best Overall Response: Part 1 [Baseline until disease progression or recurrence (actual greatest response day is up to Day 49)]

   Best overall response is the best response recorded from baseline until disease progression or recurrence. Measured as CR, PR, SD, PD, or Unknown. CR=disappearance of all primary and metastatic lesions. PR=at least a 50% decrease in primary disease measurement. SD=no new lesions; decrease of <50% in all lesions with no lesion increasing >25%. PD=any new lesion; at least a 25% increase in any disease measurement (reference smallest disease measurement recorded since start of treatment); or appearance of 1 or more new lesions. Tumor response considered Unknown if assessment prior to Day 37.

10. Percentage of Participants Exhibiting Freedom From Progression at Week 12: Part 2 [Week 12]

    Freedom from progression measured as Stable Disease (SD) or better and no Progressive Disease (PD); (CR+VGPR+Mixed Response [MR]+PR+SD). CR=disappearance of all primary and metastatic lesions. VGPR=disappearance of all metastatic lesions. MR=no new lesions; at least 50% decrease in any 1 disease measurement with <50% decrease in any other disease measurement or an increase of <25% in any lesion). SD=no new lesions; decrease of <50% in all lesions with no lesion increasing >25%. PD=at least a 25% increase in any disease measurement; or the appearance of 1 or more new lesions.

11. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 [Baseline up to EOT (within 30 days of last dose)]

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

12. Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 2 [Baseline up to EOT (within 30 days of last dose)]

    Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

13. Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 2 [Baseline up to EOT (within 30 days of last dose)]

    Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death).

14. Number of Participants Who Died: Part 2 [Baseline up to EOT (within 30 days of last dose)]

    Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs).

15. Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 2 [Baseline up to EOT (within 30 days of last dose)]

    An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported.

16. Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 2 [Baseline up to EOT (within 30 days of last dose)]

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Temporary interruption of study treatment may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor.

17. Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 2 [Baseline up to EOT (within 30 days of last dose)]

    Dose reduction for individual participant allowed if a DLT occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of >3 weeks) unless investigator and medical monitor agree participant should remain in the study.

18. Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2 [Baseline up to EOT (within 30 days of last dose)]

    Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature >39 degrees C, respiratory rate >20 bpm, and systolic and diastolic BP >200/110 mmHg. Participants may be reported in more than 1 category.

19. Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 2 [Baseline up to EOT (within 30 days of last dose)]

    Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category.

20. Maximum Observed Plasma Concentration (Cmax): Part 2 [0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

21. Average Plasma Concentration (Cavg): Part 2 [0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

22. Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 2 [0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

23. Plasma Decay Half-Life (t1/2): Part 2 [0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

    Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

24. Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 2 [0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

    AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)

25. Area Under the Concentration-time Curve at Steady State (AUCss): Part 2 [0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

    AUCss is a measure of the serum concentration of the drug at steady state. It is used to characterize drug absorption.

26. Clearance (CL): Part 2 [0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

    CL is a quantitative measure of the rate at which a drug substance is removed from the body.

27. Concentration in Plasma (Cp) and Concentration in Plasma at Time Zero (Cp Time 0): Part 1 and Part 2 [Part 1: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2; Part2: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)]

    Pharmacokinetic parameters determined in whole blood; derived from the concentration-versus-time profiles using noncompartmental analysis method. Measured as nanograms per milliliter (ng/mL).

28. Number of Participants for Change From Baseline in the Phosphorylation of Mammalian Target of Rapamycin (mTOR) Pathway Proteins: Part 1 and Part 2 [Part 1:Baseline,1,2,6,24,168 hrs post-dose of Cycle 1;additional 0 (Pre-dose),24,72,96 hrs, Day 16 to 21 of cycle 2, EOT(within 30 days of last dose); Part 2:Baseline,Day16 to 21 in Cycle 2, at time of disease progression, EOT(within 30 days of last dose)]

    Optional bone marrow sampling for pharmacodynamic analysis of effects of study treatment. Data may not be collected for a majority of patients and was not to be summarized if collection was sparse.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Inclusion Criteria:

Part 1 only:

• Subjects with a histological diagnosis of advanced cancer (solid tumors or central nervous system [CNS] tumors) with disease that is recurrent or refractory to standard therapy or for whom standard therapy is not available (histological confirmation waived for brain stem gliomas and optic pathway tumors)

Part 2 only:

• Subjects with histologically confirmed diagnosis of refractory or relapsed: Neuroblastoma, High-grade gliomas: glioblastoma multiforme, anaplastic astrocytomas, and other high-grade gliomas (histological confirmation waived for brain stem gliomas), Rhabdomyosarcoma.

• Measurable disease (for subjects with neuroblastoma, evaluable disease as determined by a positive metaiodobenzylguanidine (MIBG) scan will also be permitted).

Exclusion Criteria:

Exclusion Criteria:

• Subjects receiving enzyme-inducing anticonvulsants.

• Pulmonary hypertension or pneumonitis

• Active infection or serious intercurrent illness

• Other exclusions apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Birmingham	Alabama	United States	35233
2	Pfizer Investigational Site	San Francisco	California	United States	94143
3	Pfizer Investigational Site	Chicago	Illinois	United States	60614
4	Pfizer Investigational Site	Indianapolis	Indiana	United States	46202
5	Pfizer Investigational Site	Boston	Massachusetts	United States	02115
6	Pfizer Investigational Site	New York	New York	United States	10032
7	Pfizer Investigational Site	New York	New York	United States	11021
8	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19104-4318
9	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19104
10	Pfizer Investigational Site	Greenville	South Carolina	United States	29605
11	Pfizer Investigational Site	Memphis	Tennessee	United States	38105-2794
12	Pfizer Investigational Site	Houston	Texas	United States	77030-2399
13	Pfizer Investigational Site	Houston	Texas	United States	77030
14	Pfizer Investigational Site	Seattle	Washington	United States	98105
15	Pfizer Investigational Site	Calgary	Alberta	Canada	T3B 6A8
16	Pfizer Investigational Site	Edmonton	Alberta	Canada	T6G 2B7
17	Pfizer Investigational Site	Vancouver	British Columbia	Canada	V6H 3V4
18	Pfizer Investigational Site	Halifax,	Nova Scotia	Canada	B3K 6R8
19	Pfizer Investigational Site	London	Ontario	Canada	N6A 4G5
20	Pfizer Investigational Site	Toronto	Ontario	Canada	M5G 1X8
21	Pfizer Investigational Site	Paris Cedex 05		France	75248
22	Pfizer Investigational Site	Villejuif		France	94805
23	Pfizer Investigational Site	Muenster		Germany	48149
24	Pfizer Investigational Site	Mexico City		Mexico	04530
25	Pfizer Investigational Site	Lublin		Poland	20- 093
26	Pfizer Investigational Site	Lublin		Poland	20-093
27	Pfizer Investigational Site	Warszawa		Poland	04-730
28	Pfizer Investigational Site	Moscow		Russian Federation	115478
29	Pfizer Investigational Site	Moscow		Russian Federation	117513
30	Pfizer Investigational Site	Saint Petersburg		Russian Federation	197110

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00106353
• Other Study ID Numbers: 3066K1-139
• First Posted: Mar 23, 2005
• Last Update Posted: Feb 8, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by Pfizer: Pediatric Tumors
• Additional relevant MeSH terms: Adenocarcinoma; Sirolimus

Study Results

Participant Flow

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1	High-grade Glioma: Part 2	Neuroblastoma: Part 2	Rhabdomyosarcoma: Part 2
Arm/Group Description	Temsirolimus 10 milligram per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Period Title: Part 1
STARTED	4	5	3	7	0	0	0
COMPLETED	0	0	0	0	0	0	0
NOT COMPLETED	4	5	3	7	0	0	0
Period Title: Part 1
STARTED	0	0	0	0	17	19	16
COMPLETED	0	0	0	0	1	1	0
NOT COMPLETED	0	0	0	0	16	18	16

Baseline Characteristics

Arm/Group Title	Part 1	Part 2	Total
Arm/Group Description	Participants received temsirolimus intravenously once weekly over 60 minutes infusion in dose escalation schemes of 10 mg/m^2, 25 mg/m^2, 75 mg/m^2 and 150 mg/m^2.	Participants with high-grade glioma, neuroblastoma and rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Total of all reporting groups
Overall Participants	19	52	71
Age, Customized (participants) [Number]
Greater than or equal to(>=)1 to less than16 years	12 63.2%	42 80.8%	54 76.1%
>=16 to less than 18 years	2 10.5%	3 5.8%	5 7%
>=18 to less than or equal to 21 years	5 26.3%	7 13.5%	12 16.9%
Sex: Female, Male (Count of Participants)
Female	8 42.1%	17 32.7%	25 35.2%
Male	11 57.9%	35 67.3%	46 64.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 1
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame	Baseline up to End of Treatment (EOT) (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
AEs	4 21.1%	5 9.6%	3 4.2%	7 NaN
SAEs	2 10.5%	2 3.8%	2 2.8%	3 NaN

2. Secondary Outcome

Title	Number of Participants Who Reached Maximum Tolerated Dose Due to Dose Limiting Toxicity: Part 1
Description	Maximum tolerated dose (MTD) defined as the dose level at which >=2 of 3 participants or >=2 of 6 participants if the dose level had been expanded, experienced a dose limiting toxicity (DLT) by day 21 after the first dose of study treatment. DLT defined as failure to recover to NCI-CTCAE version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of > 3 weeks) unless the investigator and the medical monitor agree that the subject should remain in the study.
Time Frame	Baseline up to Month 6

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
Number [participants]	0 0%	0 0%	0 0%	2 NaN

3. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax): Part 1
Time Frame	0 (pre-dose), 1, 2, 6, 24, and 168 hours (hrs) post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
Cycle 1 (n = 4, 5, 3, 7)	307 (91.3)	487 (141)	480 (135)	9230 (18200)
Cycle 2 (n = 4, 4, 3, 5)	252 (98.3)	403 (128)	807 (279)	2570 (1110)

4. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 1
Time Frame	0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
Cycle 1 (n = 4, 5, 3, 7)	1 (0.143)	1.1 (0.074)	1.3 (0.231)	1.1 (0.218)
Cycle 2 (n = 4, 4, 3, 5)	1.1 (0.236)	1.7 (0.983)	1.2 (0.202)	1.2 (0.212)

5. Secondary Outcome

Title	Plasma Decay Half-Life (t1/2): Part 1
Description	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame	0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	4	3	5
Cycle 1 (n = 4, 4, 1, 4)	10.6 (0.556)	16.4 (6.9)	24 (NA)	19.3 (10.5)
Cycle 2 (n = 4, 3, 3, 5)	14.4 (4.42)	14.3 (10.4)	25.4 (1.83)	24.2 (7.58)

6. Secondary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 1
Description	AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).
Time Frame	0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
Cycle 1 (n = 4, 5, 3, 7)	1670 (730)	3890 (3190)	3750 (2420)	9680 (12800)
Cycle 2 (n = 4, 4, 3, 5)	1520 (583)	1930 (1090)	3420 (1230)	4850 (1810)

7. Secondary Outcome

Title	Area Under the Concentration-Time Curve (AUC): Part 1
Description	AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Time Frame	0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	4	3	5
Cycle 1 (n = 4, 4, 1, 4)	2000 (959)	4640 (3430)	2810 (NA)	13000 (17000)
Cycle 2 (n = 4, 3, 3, 5)	1600 (540)	2580 (768)	3500 (1140)	4960 (2000)

8. Secondary Outcome

Title	Clearance (CL): Part 1
Description	CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame	0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	4	3	5
Cycle 1 (n = 4, 4, 1, 4)	7.02 (3.68)	10.4 (6.45)	38.1 (NA)	47.9 (45.8)
Cycle 2 (n = 4, 3, 3, 5)	8.99 (5.27)	13.8 (9.06)	30.6 (15.5)	39 (24.4)

9. Secondary Outcome

Title	Volume of Distribution at Steady State (Vss): Part 1
Description	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Time Frame	0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively. Here, 'n' signifies those participants who were evaluable for particular cycle for each group respectively.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	4	3	5
Cycle 1 (n = 4, 4, 1, 4)	85.2 (35)	189 (44.2)	783 (NA)	512 (689)
Cycle 2 (n = 4, 3, 3, 5)	250 (290)	201 (132)	601 (347)	353 (130)

10. Secondary Outcome

Title	Percentage of Participants With Best Overall Response: Part 1
Description	Best overall response is the best response recorded from baseline until disease progression or recurrence. Measured as CR, PR, SD, PD, or Unknown. CR=disappearance of all primary and metastatic lesions. PR=at least a 50% decrease in primary disease measurement. SD=no new lesions; decrease of <50% in all lesions with no lesion increasing >25%. PD=any new lesion; at least a 25% increase in any disease measurement (reference smallest disease measurement recorded since start of treatment); or appearance of 1 or more new lesions. Tumor response considered Unknown if assessment prior to Day 37.
Time Frame	Baseline until disease progression or recurrence (actual greatest response day is up to Day 49)

Outcome Measure Data

Analysis Population Description

Efficacy evaluable population included all participants who received at least 3 doses of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	4	3	7
Complete response	1 5.3%	0 0%	0 0%	0 NaN
Partial response	0 0%	0 0%	0 0%	0 NaN
Stable disease	0 0%	2 3.8%	3 4.2%	2 NaN
Progressive disease	3 15.8%	2 3.8%	0 0%	3 NaN
Unknown response	0 0%	0 0%	0 0%	2 NaN

11. Secondary Outcome

Title	Percentage of Participants Exhibiting Freedom From Progression at Week 12: Part 2
Description	Freedom from progression measured as Stable Disease (SD) or better and no Progressive Disease (PD); (CR+VGPR+Mixed Response [MR]+PR+SD). CR=disappearance of all primary and metastatic lesions. VGPR=disappearance of all metastatic lesions. MR=no new lesions; at least 50% decrease in any 1 disease measurement with <50% decrease in any other disease measurement or an increase of <25% in any lesion). SD=no new lesions; decrease of <50% in all lesions with no lesion increasing >25%. PD=at least a 25% increase in any disease measurement; or the appearance of 1 or more new lesions.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Efficacy evaluable population included all participants who received at least 3 doses of study treatment. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively.

Arm/Group Title	High-grade Glioma: Part 2	Neuroblastoma: Part 2	Rhabdomyosarcoma: Part 2
Arm/Group Description	Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	15	15	12
Number (95% Confidence Interval) [percentage of participants]	46.67 245.6%	40.00 76.9%	8.33 11.7%

12. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	High-grade Glioma: Part 2	Neuroblastoma: Part 2	Rhabdomyosarcoma: Part 2
Arm/Group Description	Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	17	19	16
AEs	17 89.5%	19 36.5%	16 22.5%
SAEs	10 52.6%	6 11.5%	6 8.5%

13. Secondary Outcome

Title	Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 2
Description	Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	High-grade Glioma: Part 2	Neuroblastoma: Part 2	Rhabdomyosarcoma: Part 2
Arm/Group Description	Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	17	19	16
Number [participants]	17 89.5%	18 34.6%	13 18.3%

14. Secondary Outcome

Title	Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 2
Description	Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death).
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	High-grade Glioma: Part 2	Neuroblastoma: Part 2	Rhabdomyosarcoma: Part 2
Arm/Group Description	Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	17	19	16
Number [participants]	5 26.3%	11 21.2%	6 8.5%

15. Secondary Outcome

Title	Number of Participants Who Died: Part 2
Description	Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs).
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	High-grade Glioma: Part 2	Neuroblastoma: Part 2	Rhabdomyosarcoma: Part 2
Arm/Group Description	Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	17	19	16
Died=Yes	5 26.3%	2 3.8%	4 5.6%
Died within 30 days of last dose	3 15.8%	0 0%	3 4.2%

16. Secondary Outcome

Title	Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 2
Description	An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	High-grade Glioma: Part 2	Neuroblastoma: Part 2	Rhabdomyosarcoma: Part 2
Arm/Group Description	Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	17	19	16
Number [participants]	2 10.5%	3 5.8%	3 4.2%

17. Secondary Outcome

Title	Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 2
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Temporary interruption of study treatment may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	High-grade Glioma: Part 2	Neuroblastoma: Part 2	Rhabdomyosarcoma: Part 2
Arm/Group Description	Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	17	19	16
Number [participants]	9 47.4%	12 23.1%	6 8.5%

18. Secondary Outcome

Title	Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 2
Description	Dose reduction for individual participant allowed if a DLT occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of >3 weeks) unless investigator and medical monitor agree participant should remain in the study.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	High-grade Glioma: Part 2	Neuroblastoma: Part 2	Rhabdomyosarcoma: Part 2
Arm/Group Description	Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	17	19	16
Number [participants]	5 26.3%	10 19.2%	6 8.5%

19. Primary Outcome

Title	Number of Participants With Drug Related Treatment Emergent Adverse Events (TEAEs): Part 1
Description	TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 intravenously administered once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
Number [participants]	4 21.1%	5 9.6%	3 4.2%	7 NaN

20. Primary Outcome

Title	Number of Participants With Drug Related Grade 3 and Higher Treatment Emergent Adverse Events (TEAEs): Part 1
Description	TEAEs are events that occurred on or after initial treatment that were absent before treatment or worsened during the treatment period relative to the pretreatment state. AEs that occurred within 30 days of the last administration of study treatment can be attributed to the treatment period. National Cancer Institute (NCI)-graded Common Toxicity Criteria (CTC) provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death).
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
Number [participants]	1 5.3%	2 3.8%	2 2.8%	4 NaN

21. Primary Outcome

Title	Number of Participants Who Died: Part 1
Description	Deaths were reported from baseline throughout the 30 day period after last study treatment. After the 30 day reporting period, only deaths believed related to study treatment were to be reported (as SAEs).
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
Died=Yes	3 15.8%	1 1.9%	0 0%	0 NaN
Died within 30 days of last dose	2 10.5%	0 0%	0 0%	0 NaN

22. Primary Outcome

Title	Number of Participants With Drug Related Serious Adverse Events (SAEs): Part 1
Description	SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability / incapacity or are a congenital anomaly or birth defect in the offspring of a study subject. Participants with documented study treatment toxicity were followed weekly until recovering. After the 30 day reporting period, only SAEs believed to be related to study treatment were to be reported.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
Number [participants]	0 0%	0 0%	0 0%	1 NaN

23. Primary Outcome

Title	Number of Participants With Adverse Events Causing Temporary Stop of Study Treatment: Part 1
Description	Temporary interruption of study treatment; may be followed by resumption of study treatment at current dose or dose modification as determined by the investigator and medical monitor.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
Number [participants]	0 0%	2 3.8%	1 1.4%	2 NaN

24. Primary Outcome

Title	Number of Participants With Adverse Events Causing Dose Reduction of Study Treatment: Part 1
Description	Dose reduction for individual participant allowed if a dose limiting toxicity (DLT) occurred; may continue treatment following reduction by 1 to 2 dose levels (determined by investigator and medical monitor). DLT= failure to recover to National Cancer Institute Common Terminology Criteria for AEs (NCI-CTCAE) version 3.0 grade 0 to 2 (or within 1 grade of starting values for pre-existing laboratory abnormalities) from a treatment-related toxicity within 3 weeks (leading to a treatment delay of >3 weeks) unless investigator and medical monitor agree participant should remain in the study.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
Number [participants]	0 0%	0 0%	0 0%	1 NaN

25. Primary Outcome

Title	Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 1
Description	Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature >39 degrees Celsius (C), respiratory rate >20 beats per minute (bpm), and systolic and diastolic blood pressure (BP) >200/110 millimeters of mercury (mmHg). Participants may be reported in more than 1 category.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 administered intravenously once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
Temperature >39 degrees C	1 5.3%	2 3.8%	1 1.4%	3 NaN
Respiratory rate >20 bpm	4 21.1%	5 9.6%	3 4.2%	7 NaN
Systolic/Diastolic BP >200/110 mmHg	0 0%	0 0%	0 0%	0 NaN

26. Secondary Outcome

Title	Number of Participants With Potentially Clinically Important (PCI) Changes in Vital Signs: Part 2
Description	Number of participants who met the criteria for PCI changes (based on baseline values before treatment); criteria defined as body temperature >39 degrees C, respiratory rate >20 bpm, and systolic and diastolic BP >200/110 mmHg. Participants may be reported in more than 1 category.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	High-grade Glioma: Part 2	Neuroblastoma: Part 2	Rhabdomyosarcoma: Part 2
Arm/Group Description	Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	17	19	16
Temperature >39 degrees C	0 0%	0 0%	0 0%
Respiratory rate >20 bpm	16 84.2%	18 34.6%	14 19.7%
Systolic/Diastolic BP >200/110 mmHg	1 5.3%	0 0%	0 0%

27. Secondary Outcome

Title	Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 2
Description	Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	High-grade Glioma: Part 2	Neuroblastoma: Part 2	Rhabdomyosarcoma: Part 2
Arm/Group Description	Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	17	19	16
Number [participants]	17 89.5%	19 36.5%	15 21.1%

28. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax): Part 2
Time Frame	0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Part 2
Arm/Group Description	Participants with high-grade glioma, neuroblastoma and rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion..
Measure Participants	35
Mean (Standard Deviation) [ng/mL]	6280 (21000)

29. Secondary Outcome

Title	Average Plasma Concentration (Cavg): Part 2
Time Frame	0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Part 2
Arm/Group Description	Participants with high-grade glioma, neuroblastoma and rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	31
Mean (Standard Deviation) [ng/mL]	82.8 (143)

30. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax): Part 2
Time Frame	0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Part 2
Arm/Group Description	Participants with high-grade glioma, neuroblastoma and rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	35
Median (Full Range) [hr]	1.00

31. Secondary Outcome

Title	Plasma Decay Half-Life (t1/2): Part 2
Description	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame	0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for.

Arm/Group Title	Part 2
Arm/Group Description	Participants with high-grade glioma, neuroblastoma and rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	26
Mean (Standard Deviation) [hr]	30.65 (13.63)

32. Secondary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-t)]: Part 2
Description	AUC (0-t)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t)
Time Frame	0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Part 2
Arm/Group Description	Participants with high-grade glioma, neuroblastoma and rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	35
Mean (Standard Deviation) [hr*ng/mL]	13100 (22700)

33. Primary Outcome

Title	Number of Participants With Potentially Clinically Important (PCI) Values by National Cancer Institute Common Terminology Criteria (NCI-CTC) Grade for Laboratory Values: Part 1
Description	Number of participants who met the PCI criteria (grades 1 through 5) for laboratory values (hematology and serum chemistry). NCI-CTC provides descriptive terminology for adverse event reporting. A grading (severity) scale is provided with grades ranging from 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening or disabling), to 5 (death). Participants may be reported in more than 1 category.
Time Frame	Baseline up to EOT (within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication.

Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1	Temsirolimus 25 mg/m^2: Part 1	Temsirolimus 75 mg/m^2: Part 1	Temsirolimus 150 mg/m^2: Part 1
Arm/Group Description	Temsirolimus 10 milligrams per square meter (mg/m^2) administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 25 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 75 mg/m^2 administered intravenously once weekly over 60 minutes infusion.	Temsirolimus 150 mg/m^2 intravenously administered once weekly over 60 minutes infusion.
Measure Participants	4	5	3	7
Number [participants]	4 21.1%	5 9.6%	3 4.2%	7 NaN

34. Primary Outcome

Title	Percentage of Participants With Objective Response (OR) at Week 12: Part 2
Description	Measured as Complete response (CR), Very good partial response (VGPR), or Partial response (PR) on at least 2 occasions greater than or equal to (>=) 4 weeks apart within first 12 weeks. CR=disappearance of all primary and metastatic lesions; Homovanillic acid, Vanillymandelic acid (HVA/VMA) normal; bone marrow immunocytology negative. VGPR=disappearance of all metastatic lesions (residual areas of uptake on bone permitted); 90 to 99 percent (%) decrease in primary disease measurement; HVA/VMA normal or both decreased >90%. PR=at least 50% decrease in primary and metastatic disease. Number of bone sites decreased by at least 50%.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Efficacy evaluable population included all participants who received at least 3 doses of study treatment. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure for each group respectively.

Arm/Group Title	High-grade Glioma: Part 2	Neuroblastoma: Part 2	Rhabdomyosarcoma: Part 2
Arm/Group Description	Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.	Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	15	15	12
Number [percentage of participants]	0.00 0%	6.67 12.8%	0.00 0%

35. Secondary Outcome

Title	Area Under the Concentration-time Curve at Steady State (AUCss): Part 2
Description	AUCss is a measure of the serum concentration of the drug at steady state. It is used to characterize drug absorption.
Time Frame	0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Part 2
Arm/Group Description	Participants with high-grade glioma, neuroblastoma and rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	31
Mean (Standard Deviation) [hr*ng/mL]	13900 (24100)

36. Secondary Outcome

Title	Clearance (CL): Part 2
Description	CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame	0 (pre-dose),1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of study medication. Here, the 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Part 2
Arm/Group Description	Participants with high-grade glioma, neuroblastoma and rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	31
Mean (Standard Deviation) [L/hr]	14.3 (14.0)

37. Secondary Outcome

Title	Concentration in Plasma (Cp) and Concentration in Plasma at Time Zero (Cp Time 0): Part 1 and Part 2
Description	Pharmacokinetic parameters determined in whole blood; derived from the concentration-versus-time profiles using noncompartmental analysis method. Measured as nanograms per milliliter (ng/mL).
Time Frame	Part 1: 0 (pre-dose), 1, 2, 6, 24, and 168 hrs post-dose of Cycle 1 and 0 (pre-dose), 1, 2, 6, 24, 72, 96, and 168 hrs post-dose of Cycle 2; Part2: 0 (pre-dose), 1, 6, 24, 48, 72, 96, and 168 hrs post-dose of Cycle 2 (cycles are approximately 21 days)

Outcome Measure Data

Analysis Population Description

Data was not analyzed.

Arm/Group Title	Part 1	Part 2
Arm/Group Description	Participants received temsirolimus intravenously once weekly over 60 minutes infusion in dose escalation schemes of 10 mg/m^2, 25 mg/m^2, 75 mg/m^2 and 150 mg/m^2.	Participants with high-grade glioma, neuroblastoma and rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	0	0

38. Secondary Outcome

Title	Number of Participants for Change From Baseline in the Phosphorylation of Mammalian Target of Rapamycin (mTOR) Pathway Proteins: Part 1 and Part 2
Description	Optional bone marrow sampling for pharmacodynamic analysis of effects of study treatment. Data may not be collected for a majority of patients and was not to be summarized if collection was sparse.
Time Frame	Part 1:Baseline,1,2,6,24,168 hrs post-dose of Cycle 1;additional 0 (Pre-dose),24,72,96 hrs, Day 16 to 21 of cycle 2, EOT(within 30 days of last dose); Part 2:Baseline,Day16 to 21 in Cycle 2, at time of disease progression, EOT(within 30 days of last dose)

Outcome Measure Data

Analysis Population Description

Data was not analyzed.

Arm/Group Title	Part 1	Part 2
Arm/Group Description	Participants received temsirolimus intravenously once weekly over 60 minutes infusion in dose escalation schemes of 10 mg/m^2, 25 mg/m^2, 75 mg/m^2 and 150 mg/m^2.	Participants with high-grade glioma, neuroblastoma and rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Temsirolimus 10 mg/m^2: Part 1		Temsirolimus 25 mg/m^2: Part 1		Temsirolimus 75 mg/m^2: Part 1		Temsirolimus 150 mg/m^2: Part 1		High-grade Glioma: Part 2		Neuroblastoma: Part 2		Rhabdomyosarcoma: Part 2
Arm/Group Description	Temsirolimus 10 mg/m^2 administered intravenously once weekly over 60 minutes infusion.		Temsirolimus 25 mg/m^2 intravenously administered once weekly over 60 minutes infusion.		Temsirolimus 75 mg/m^2 intravenously administered once weekly over 60 minutes infusion.		Temsirolimus 150 mg/m^2 intravenously administered once weekly over 60 minutes infusion.		Participants with high-grade glioma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.		Participants with neuroblastoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.		Participants with rhabdomyosarcoma were administered temsirolimus 75 mg/m^2 intravenously once weekly over 60 minutes infusion.
All Cause Mortality
	Temsirolimus 10 mg/m^2: Part 1		Temsirolimus 25 mg/m^2: Part 1		Temsirolimus 75 mg/m^2: Part 1		Temsirolimus 150 mg/m^2: Part 1		High-grade Glioma: Part 2		Neuroblastoma: Part 2		Rhabdomyosarcoma: Part 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Temsirolimus 10 mg/m^2: Part 1		Temsirolimus 25 mg/m^2: Part 1		Temsirolimus 75 mg/m^2: Part 1		Temsirolimus 150 mg/m^2: Part 1		High-grade Glioma: Part 2		Neuroblastoma: Part 2		Rhabdomyosarcoma: Part 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50%)		2/5 (40%)		2/3 (66.7%)		3/7 (42.9%)		10/17 (58.8%)		6/19 (31.6%)		6/16 (37.5%)
Blood and lymphatic system disorders
Anaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Thrombocytopenia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Cardiac disorders
Hypotension	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Shock	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Left ventricular dysfunction	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Endocrine disorders
Inappropriate antidiuretic hormone secretion	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Gastrointestinal disorders
Vomiting	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Colitis	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Nausea	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Stomatitis	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Salivary hypersecretion	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Vomiting	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
General disorders
Pain	1/4 (25%)		0/5 (0%)		1/3 (33.3%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Fever	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Sarcoma	1/4 (25%)		1/5 (20%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Abdominal pain	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Chest pain	0/4 (0%)		1/5 (20%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Headache	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Infection	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Sepsis	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Fatigue	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Oedema peripheral	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Pyrexia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		0/16 (0%)
Infections and infestations
Abscess	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Bacteraemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Nail infection	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Osteomyelitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Pneumonia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		1/16 (6.3%)
Sepsis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Injury, poisoning and procedural complications
Brain herniation	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Metabolism and nutrition disorders
Dehydration	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Hyperglycaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Hyponatraemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Hypophosphataemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rhabdomyosarcoma	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Tumour pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Nervous system disorders
Convulsion	0/4 (0%)		1/5 (20%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Grand mal convulsion	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Paresis	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Cerebral haemorrhage	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Coordination abnormal	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Drooling	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Grand mal convulsion	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Headache	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Somnolence	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Renal and urinary disorders
Urinary retention	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/4 (0%)		1/5 (20%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Pneumonia	0/4 (0%)		1/5 (20%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Cough	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Dyspnoea	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Haemothorax	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Hypoxia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		1/16 (6.3%)
Interstitial lung disease	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Pneumonitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		0/16 (0%)
Pulmonary embolism	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Respiratory distress	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		1/16 (6.3%)
Skin and subcutaneous tissue disorders
Rash	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Vascular disorders
Deep vein thrombosis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		0/19 (0%)		0/16 (0%)
Thrombosis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Temsirolimus 10 mg/m^2: Part 1		Temsirolimus 25 mg/m^2: Part 1		Temsirolimus 75 mg/m^2: Part 1		Temsirolimus 150 mg/m^2: Part 1		High-grade Glioma: Part 2		Neuroblastoma: Part 2		Rhabdomyosarcoma: Part 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		5/5 (100%)		3/3 (100%)		7/7 (100%)		17/17 (100%)		19/19 (100%)		15/16 (93.8%)
Blood and lymphatic system disorders
Anemia	3/4 (75%)		0/5 (0%)		2/3 (66.7%)		6/7 (85.7%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Thrombocytopenia	2/4 (50%)		2/5 (40%)		3/3 (100%)		4/7 (57.1%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Leukopenia	1/4 (25%)		1/5 (20%)		3/3 (100%)		5/7 (71.4%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Neutropenia	0/4 (0%)		2/5 (40%)		3/3 (100%)		4/7 (57.1%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
International normalised ratio increased	1/4 (25%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Activated partial thromboplastin time prolonged	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Ecchymosis	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Fibrinogen increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hemolysis	0/4 (0%)		1/5 (20%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Leukocytosis	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Lymphopenia	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Anaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		5/19 (26.3%)		2/16 (12.5%)
Leukopenia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		4/19 (21.1%)		5/16 (31.3%)
Lymphopenia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		2/19 (10.5%)		1/16 (6.3%)
Neutropenia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		3/19 (15.8%)		1/16 (6.3%)
Thrombocytopenia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		5/17 (29.4%)		6/19 (31.6%)		6/16 (37.5%)
Cardiac disorders
Hypotension	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Pericardial effusion	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Syncope	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Cyanosis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Pericardial effusion	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Tachycardia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		3/16 (18.8%)
Ear and labyrinth disorders
Ear pain	1/4 (25%)		0/5 (0%)		1/3 (33.3%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Cerumen impaction	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Ear pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Otorrhoea	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Tympanic membrane perforation	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Vertigo	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Endocrine disorders
Glycosuria	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Cushingoid	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Eye disorders
Conjunctival injection	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Eye pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Lacrimation disorder	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Abnormal vision	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Conjunctivitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		3/19 (15.8%)		1/16 (6.3%)
Exophthalmos	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Eye pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Ocular hyperaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Periorbital oedema	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Visual acuity reduced	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Gastrointestinal disorders
Vomiting	3/4 (75%)		2/5 (40%)		1/3 (33.3%)		4/7 (57.1%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Anorexia	2/4 (50%)		0/5 (0%)		1/3 (33.3%)		6/7 (85.7%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Mucositis	2/4 (50%)		1/5 (20%)		1/3 (33.3%)		3/7 (42.9%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Nausea	0/4 (0%)		1/5 (20%)		2/3 (66.7%)		4/7 (57.1%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Diarrhoea	1/4 (25%)		1/5 (20%)		2/3 (66.7%)		2/7 (28.6%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Constipation	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		2/7 (28.6%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Esophagitis	0/4 (0%)		1/5 (20%)		1/3 (33.3%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Oral moniliasis	0/4 (0%)		0/5 (0%)		2/3 (66.7%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Cheilitis	1/4 (25%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Colitis	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Gamma glutamyl transpeptidase increased	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Rectal disorder	0/4 (0%)		1/5 (20%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Abdominal distension	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Abdominal pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		6/19 (31.6%)		2/16 (12.5%)
Abdominal pain upper	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		0/19 (0%)		1/16 (6.3%)
Aphthous stomatitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Breath odour	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Constipation	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		5/19 (26.3%)		0/16 (0%)
Diarrhoea	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		4/17 (23.5%)		2/19 (10.5%)		1/16 (6.3%)
Dyspepsia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Dysphagia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Eructation	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Flatulence	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Gastrointestinal pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Gingival bleeding	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Gingivitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Glossitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Lip dry	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Nausea	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		4/19 (21.1%)		4/16 (25%)
Oesophageal pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		1/16 (6.3%)
Oral disorder	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Periodontal disease	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Rectal discharge	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Stomatitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		5/19 (26.3%)		3/16 (18.8%)
Tooth impacted	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Toothache	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Vomiting	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		5/17 (29.4%)		2/19 (10.5%)		1/16 (6.3%)
General disorders
Pain	2/4 (50%)		2/5 (40%)		3/3 (100%)		2/7 (28.6%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Fever	0/4 (0%)		2/5 (40%)		1/3 (33.3%)		4/7 (57.1%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Infection	1/4 (25%)		1/5 (20%)		2/3 (66.7%)		3/7 (42.9%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Asthenia	1/4 (25%)		1/5 (20%)		0/3 (0%)		4/7 (57.1%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Headache	0/4 (0%)		2/5 (40%)		1/3 (33.3%)		3/7 (42.9%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Abdominal pain	0/4 (0%)		1/5 (20%)		1/3 (33.3%)		2/7 (28.6%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Allergic reaction	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Back pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		2/7 (28.6%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Face edema	1/4 (25%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Accidental injury	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Cellulitis	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Chest pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Injection site reaction	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Asthenia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		3/19 (15.8%)		1/16 (6.3%)
Axillary pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Catheter site rash	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Chest pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		1/16 (6.3%)
Device occlusion	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Fatigue	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		6/17 (35.3%)		6/19 (31.6%)		5/16 (31.3%)
Gait disturbance	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Injection site haematoma	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Irritability	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Mucosal inflammation	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		3/17 (17.6%)		0/19 (0%)		1/16 (6.3%)
Oedema peripheral	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		2/16 (12.5%)
Pyrexia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		9/19 (47.4%)		4/16 (25%)
Ulcer	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Hepatobiliary disorders
Cholelithiasis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Hepatomegaly	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Immune system disorders
Hypersensitivity	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Infections and infestations
Abscess	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Acne pustular	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Bronchitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Cellulitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		0/19 (0%)		0/16 (0%)
Cystitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Device related infection	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Ear infection	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		1/16 (6.3%)
Folliculitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Fungal skin infection	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Gastroenteritis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		1/19 (5.3%)		0/16 (0%)
Herpes simplex	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Infection	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Laryngitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Lobar pneumonia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Localised infection	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Lung infection	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Nail infection	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Nasopharyngitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Oesophageal candidiasis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Oral candidiasis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		3/17 (17.6%)		1/19 (5.3%)		0/16 (0%)
Oral herpes	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Osteomyelitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Otitis externa	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Parainfluenzae virus infection	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Paronychia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		0/16 (0%)
Pharyngitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Pneumonia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Pyoderma	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Rhinitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		4/19 (21.1%)		0/16 (0%)
Sinusitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Staphylococcal infection	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Upper respiratory tract infection	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		5/19 (26.3%)		2/16 (12.5%)
Urinary tract infection	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		0/19 (0%)		0/16 (0%)
Injury, poisoning and procedural complications
Animal bite	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Arthropod bite	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Contusion	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Excoriation	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Head injury	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Humerus fracture	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Procedural pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Radiation injury	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Sunburn	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Investigations
Local reaction to procedure	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Alanine aminotransferase increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		6/17 (35.3%)		7/19 (36.8%)		1/16 (6.3%)
Aspartate aminotransferase increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		3/17 (17.6%)		6/19 (31.6%)		5/16 (31.3%)
Blood albumin decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Blood alkaline phosphatase increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		4/19 (21.1%)		0/16 (0%)
Blood bicarbonate decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		1/16 (6.3%)
Blood bilirubin increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Blood calcium decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		0/16 (0%)
Blood cholesterol increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		3/17 (17.6%)		6/19 (31.6%)		1/16 (6.3%)
Blood creatinine increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		3/19 (15.8%)		0/16 (0%)
Blood fibrinogen increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Blood glucose decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Blood glucose increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		4/19 (21.1%)		1/16 (6.3%)
Blood lactate dehydrogenase increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Blood magnesium increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		3/19 (15.8%)		1/16 (6.3%)
Blood phosphorus decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		3/19 (15.8%)		1/16 (6.3%)
Blood potassium decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		4/19 (21.1%)		0/16 (0%)
Blood potassium increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Blood pressure decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Blood sodium decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		2/19 (10.5%)		0/16 (0%)
Blood triglycerides increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		4/17 (23.5%)		6/19 (31.6%)		2/16 (12.5%)
Blood urea increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Cardiac murmur	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Electrocardiogram QT prolonged	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Glycosylated haemoglobin increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Haemoglobin decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		6/19 (31.6%)		1/16 (6.3%)
High density lipoprotein decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Lipase increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Low density lipoprotein increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Neutrophil count decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		4/19 (21.1%)		0/16 (0%)
Platelet count decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		4/17 (23.5%)		7/19 (36.8%)		2/16 (12.5%)
Respiratory rate	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Weight decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		3/16 (18.8%)
Weight increased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
White blood cell count decreased	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		5/19 (26.3%)		1/16 (6.3%)
Metabolism and nutrition disorders
Hypoproteinemia	2/4 (50%)		1/5 (20%)		2/3 (66.7%)		4/7 (57.1%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hyperglycemia	0/4 (0%)		3/5 (60%)		1/3 (33.3%)		4/7 (57.1%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hyperlipemia	1/4 (25%)		3/5 (60%)		2/3 (66.7%)		2/7 (28.6%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hypokalemia	2/4 (50%)		1/5 (20%)		2/3 (66.7%)		3/7 (42.9%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
SGOT increased	2/4 (50%)		2/5 (40%)		2/3 (66.7%)		2/7 (28.6%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hypercholesteremia	0/4 (0%)		2/5 (40%)		1/3 (33.3%)		4/7 (57.1%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hypophosphatemia	0/4 (0%)		1/5 (20%)		2/3 (66.7%)		2/7 (28.6%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hyponatremia	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		3/7 (42.9%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
SGPT increased	1/4 (25%)		0/5 (0%)		2/3 (66.7%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Alkaline phosphatase increased	1/4 (25%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Bilirubinemia	0/4 (0%)		1/5 (20%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hypermagnesemia	1/4 (25%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hypoglycemia	0/4 (0%)		1/5 (20%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Weight loss	1/4 (25%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Creatinine increased	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Dehydration	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hypercalcemia	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hypernatremia	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hypocalcemia	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hypomagnesemia	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Peripheral edema	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Acidosis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Decreased appetite	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		3/17 (17.6%)		6/19 (31.6%)		5/16 (31.3%)
Dehydration	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Hypercalcaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		1/16 (6.3%)
Hypercholesterolaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		3/17 (17.6%)		2/19 (10.5%)		0/16 (0%)
Hyperglycaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		2/19 (10.5%)		3/16 (18.8%)
Hypermagnesaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Hypertriglyceridaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		2/16 (12.5%)
Hypoalbuminaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		3/16 (18.8%)
Hypocalcaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		1/16 (6.3%)
Hypochloraemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Hypoglycaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		1/16 (6.3%)
Hypokalaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		4/19 (21.1%)		3/16 (18.8%)
Hypomagnesaemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		1/16 (6.3%)
Hyponatraemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Hypophosphataemia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		6/19 (31.6%)		0/16 (0%)
Polydipsia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Muscle spasms	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Arthralgia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		6/19 (31.6%)		2/16 (12.5%)
Back pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		4/19 (21.1%)		2/16 (12.5%)
Bone pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Muscle spasms	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		2/19 (10.5%)		0/16 (0%)
Muscle twitching	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Muscular weakness	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		1/16 (6.3%)
Musculoskeletal chest pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Musculoskeletal pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		2/19 (10.5%)		2/16 (12.5%)
Myalgia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Neck pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		1/16 (6.3%)
Pain in extremity	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		5/19 (26.3%)		2/16 (12.5%)
Pain in jaw	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroblastoma	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Tumour pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Nervous system disorders
Neuropathy	1/4 (25%)		2/5 (40%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Depression	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hostility	0/4 (0%)		0/5 (0%)		0/3 (0%)		2/7 (28.6%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Convulsion	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Dizziness	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hypesthesia	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Insomnia	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Paresthesia	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Accessory nerve disorder	0/4 (0%)		0/5 (0%)		0/3 (0%)	0	0/7 (0%)	0	1/17 (5.9%)	0	0/19 (0%)	0	0/16 (0%)	0
Ataxia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		0/19 (0%)		0/16 (0%)
Cerebral haemorrhage	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Dizziness	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		0/16 (0%)
Dyskinesia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Headache	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		3/17 (17.6%)		4/19 (21.1%)		4/16 (25%)
Hemiparesis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Hyperaesthesia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Hypoaesthesia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		0/19 (0%)		1/16 (6.3%)
Partial seizures	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Peripheral motor neuropathy	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Peripheral sensory neuropathy	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		0/16 (0%)
Somnolence	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Spinal cord compression	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Psychiatric disorders
Agitation	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Anxiety	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		1/19 (5.3%)		4/16 (25%)
Attention deficit/hyperactivity disorder	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Confusional state	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Depression	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Insomnia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		0/16 (0%)
Mood altered	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		0/16 (0%)
Sleep disorder	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		0/16 (0%)
Renal and urinary disorders
Urinary frequency	0/4 (0%)		3/5 (60%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Dysuria	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hematuria	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Chromaturia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Dysuria	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Glycosuria	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		1/16 (6.3%)
Haematuria	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		1/16 (6.3%)
Proteinuria	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		3/19 (15.8%)		1/16 (6.3%)
Urethral pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Urinary retention	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		1/19 (5.3%)		0/16 (0%)
Urogenital haemorrhage	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Reproductive system and breast disorders
Pelvic pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Cough increased	2/4 (50%)		1/5 (20%)		1/3 (33.3%)		3/7 (42.9%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Rhinitis	0/4 (0%)		1/5 (20%)		0/3 (0%)		2/7 (28.6%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Dyspnea	1/4 (25%)		1/5 (20%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Pleural effusion	1/4 (25%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Rhinitis allergic	1/4 (25%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Upper respiratory infection	1/4 (25%)		1/5 (20%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Asthma	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Epistaxis	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Hemoptysis	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Laryngitis	0/4 (0%)		1/5 (20%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Lung hemorrhage	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Pharyngitis	1/4 (25%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Pneumothorax	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Sinusitis	0/4 (0%)		1/5 (20%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Tachypnoea	0/4 (0%)		1/5 (20%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Atelectasis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Bronchial obstruction	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Bronchospasm	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		1/16 (6.3%)
Cough	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		5/17 (29.4%)		6/19 (31.6%)		3/16 (18.8%)
Dysphonia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Dyspnoea	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		2/19 (10.5%)		4/16 (25%)
Epistaxis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		2/16 (12.5%)
Hypoxia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		3/16 (18.8%)
Lung infiltration	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Oropharyngeal pain	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		4/19 (21.1%)		1/16 (6.3%)
Pharyngeal erythema	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Pharyngeal inflammation	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Pleural effusion	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Pneumonitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Rhinitis allergic	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Rhinorrhoea	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		2/19 (10.5%)		1/16 (6.3%)
Suffocation feeling	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Upper-airway cough syndrome	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Skin and subcutaneous tissue disorders
Rash	1/4 (25%)		1/5 (20%)		1/3 (33.3%)		4/7 (57.1%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Alopecia	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Herpes simplex	0/4 (0%)		1/5 (20%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Pruritus	0/4 (0%)		0/5 (0%)		2/3 (66.7%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Acne	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Application site reaction	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Dry skin	0/4 (0%)		0/5 (0%)		1/3 (33.3%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Exfoliative dermatitis	0/4 (0%)		0/5 (0%)		0/3 (0%)		1/7 (14.3%)		0/17 (0%)		0/19 (0%)		0/16 (0%)
Acne	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		2/17 (11.8%)		0/19 (0%)		1/16 (6.3%)
Alopecia	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		0/16 (0%)
Dermatitis acneiform	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Dermatitis allergic	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Dry skin	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		3/19 (15.8%)		2/16 (12.5%)
Ecchymosis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Exfoliative rash	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Hyperhidrosis	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		0/19 (0%)		1/16 (6.3%)
Nail bed inflammation	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Nail bed tenderness	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Nail disorder	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		0/16 (0%)
Pruritus	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		3/19 (15.8%)		1/16 (6.3%)
Rash	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		5/17 (29.4%)		3/19 (15.8%)		2/16 (12.5%)
Rash erythematous	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Rash follicular	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Rash pruritic	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Scab	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Skin disorder	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Skin lesion	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		1/19 (5.3%)		0/16 (0%)
Surgical and medical procedures
Nail operation	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Vascular disorders
Flushing	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		1/17 (5.9%)		0/19 (0%)		0/16 (0%)
Haematoma	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		1/19 (5.3%)		0/16 (0%)
Hypertension	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		3/17 (17.6%)		1/19 (5.3%)		2/16 (12.5%)
Hypotension	0/4 (0%)		0/5 (0%)		0/3 (0%)		0/7 (0%)		0/17 (0%)		2/19 (10.5%)		1/16 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.