A Study of the Effect of R1507 in Combination With Tarceva (Erlotinib) on Progression-Free Survival in Patients With Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC) Having Received Tarceva Monotherapy.

• Sponsor: Hoffmann-La Roche (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00773383
• Collaborator: (none)
• Enrollment: 35
• Locations: 16
• Arm: 1
• Duration (Months): 15
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This single arm study in patients with advanced Stage IIIb/IV NSCLC who have progressive disease after deriving clinical benefit (defined as response or stable disease after 12 weeks) from second or third line Tarceva monotherapy will determine the proportion of patients with progression-free survival at 12 weeks following combination therapy with R1507 and Tarceva. Patients will receive R1507 (9mg/kg iv) weekly in combination with Tarceva (150mg oral daily) for up to a maximum of 24 months. Other disease-related endpoints including overall survival, objective response rate, time to response, time to progressive disease and duration of response will also be evaluated. The anticipated time on study treatment is 1-2 years, and the target sample size is <100 individuals.

Condition or Disease	Intervention/Treatment	Phase
Non-Small Cell Lung Cancer	Drug: RG1507; Drug: erlotinib [Tarceva]	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Study to Determine the Effect of R1507 Plus Tarceva (Erlotinib) on Progression-free Survival in Patients With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) With Progressive Disease After Clinical Benefit to Second or Third Line Tarceva Monotherapy.
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: RG1507; iv 9mg/kg weekly; Drug: erlotinib [Tarceva]; 150mg oral daily

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Progression Free Survival (PFS) [12 weeks]

   The primary efficacy endpoint is progression-free survival at 12 weeks after start of therapy. A progression-free survival rate at 12 weeks will be calculated, with patients categorized in a dichotomous manner as alive and progression-free or in progression or dead at 12 weeks.

Secondary Outcome Measures

1. Duration of Overall Survival [From start of treatment to death; up to the time that all participants ended treatment]

   The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.

2. Participants Achieving Objective Response [Patients were followed from start of therapy until date of first response]

   Objective response is defined as a complete response (CR) or partial response (PR) that has been confirmed by a second tumor assessment no earlier than 4 weeks after the initial documentation. Response is assessed using Response Evaluation Criteria in Solid Tumors (RECIST)criteria. The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.

3. Time to Best Response [Patients were followed from start of therapy until date of first response]

   This is defined as time from the start of therapy to the date of first CR or PR. The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.

4. Time to Progressive Disease (PD) [From start of therapy to the date of first documentation of PD. Pts who never progress prior to final analysis or are withdrawn from the study without documented progression will be censored at the date of the last valid tumor assessment.]

   The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.

5. Duration of Objective Response [from the date the complete or partial response was first recorded to the date which progressive disease is first noted or date of death. If a patient does not progress or die while being followed, the date of the last valid tumor assessment will be taken]

   This is defined similarly for complete and partial responders. Complete response or partial response lasts from the date the complete response or partial response was first recorded to the date on which progressive disease is first noted or date of death. If a patient does not progress or die while being followed, the date of the last valid tumor assessment will be taken. The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.

6. Baseline Electrocardiogram (ECG) [baseline within 28 days of starting treatment (screening visit).]

   Standard safety monitoring includes baseline Electrocardiogram (ECG). The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed. The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.

7. Fasting Glucose, Highest Post-Baseline Value [Baseline, Highest Post-Baseline value within the timeframe of post-baseline collection up to when patient discontinued (up to 59 weeks)]

   A fasting glucose was required at baseline, and random non-fasting glucose testing was performed weekly for the first 6 weeks followed by day 1 of each 3 week treatment phase. The number of participants with the highest post-baseline fasting glucose level at any time point post baseline relative to the participant's baseline glucose level is reported.

8. Hemoglobin A1c (HbA1c) [screening]

   Standard safety monitoring includes baseline Electrocardiogram (ECG), Fasting glucose and HbA1c, monthly urine pregnancy test in female patients of childbearing potential and Human anti-human antibody (HAHA) testing. Data will be represented in the Serious Adverse Event (SAE) Adverse Event (AE) section of Protocol Registration System (PRS).

9. Monthly Urine Pregnancy Test in Female Patients of Childbearing Potential [Within 7 days of starting treatment (baseline visit)]

   Standard safety monitoring includes baseline Electrocardiogram (ECG), Fasting glucose and HbA1c, monthly urine pregnancy test in female patients of childbearing potential and Human anti-human antibody (HAHA) testing. Not posted; it will be represented in the Serious Adverse Event (SAE) Adverse Event (AE) section of Protocol Registration System (PRS).

10. Number of Participants With Positive Results for Human Anti-human Antibody (HAHA) Testing [prior to dosing on week 1 (day 1), week 4 (day 22), week 10 (day 64), final visit, follow up visit and 12 weeks post last dose (up to 71 weeks)]

    Number of participants who tested positive for Human anti-human antibody (HAHA) testing for immunogenicity. To determine HAHA specificity, screened positive samples were tested in a confirmatory assay in the presence of 10 ug/mL R1507. Samples with > 19.7% inhibition were considered true positives, whereas those with < 19.7% inhibition were considered to be false positives.

11. Electrocardiogram (ECG) [baseline and thereafter as clinically indicated at the discretion of the investigator up to the time that the patient discontinued (up to 59 weeks)]

    12 lead ECG is required at baseline and will be measured during the trial as clinically indicated at the discretion of the investigators. For each reading, QTcF value will be calculated as the QT value (seconds) divided by the cube root of the RR interval in seconds (Fridericia correction). A listing will be generated showing, for each patient, the visits at which ECGs were taken and the results (normal or abnormal, as well as any comments provided).

12. Population Pharmacokinetics of R1507 and Tarceva [Throughout study]

    Population PK of R1507 and erlotinib were planned but not analyzed due to the termination of the trial.

13. Assessment of Potential Predictive and Prognostic Biomarkers. [Throughout study]

    Total IGF-I, free IGF I/II and other potential biomarkers present in serum. Further putative biomarker analyses in blood and tumor samples were planned in the protocol for exploratory assessment of correlation with clinical outcome. None of these were analyzed due to the termination of the trial.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• male or female patients >=18 years with histologically documented inoperable, locally advanced or metastatic (stage IIIB or IV) NSCLC;

• currently receiving Tarceva monotherapy and having failed at least one standard chemotherapy regimens;

• prior response or stable disease 12 weeks from start of Tarceva;

• documented progressive disease at enrollment;

• measurable disease according to the RECIST criteria;

• ECOG performance status 0-2;

• life expectancy >12 weeks.

Exclusion Criteria:

• patients with active CNS lesions;

• prior treatment with agents acting via IGF-1R inhibition or EGFR targeting;

• administration with high doses of systemic corticosteroids;

• radiotherapy in the 4 weeks prior to study start;

• surgery or significant traumatic injury with in the last 2 weeks prior to study start.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Santa Monica	California	United States	90404
2		Miami	Florida	United States	33101
3		Boston	Massachusetts	United States	02114
4		Boston	Massachusetts	United States	02115
5		Boston	Massachusetts	United States	02215
6		Hickory	North Carolina	United States	28602
7		Calgary	Alberta	Canada	T2N 4N2
8		Ottawa	Ontario	Canada	K1H 8L6
9		Montreal	Quebec	Canada	H3A 1A1
10		Montreal	Quebec	Canada	H3G 1A4
11		Marseille		France	13015
12		Paris		France	75230
13		Villejuif		France	94805
14		Gdansk		Poland	80-211
15		Lublin		Poland	20-950
16		Poznan		Poland	60-569

Sponsors and Collaborators

• Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00773383
• Other Study ID Numbers: NO21746; 2008-001762-85
• First Posted: Oct 16, 2008
• Last Update Posted: Jun 24, 2013
• Last Verified: Jun 1, 2013

• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Erlotinib Hydrochloride

Study Results

Participant Flow

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Period Title: Overall Study
STARTED	35
Received Study Drug	34
COMPLETED	4
NOT COMPLETED	31

Baseline Characteristics

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Overall Participants	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.9 (11.43)
Sex: Female, Male (Count of Participants)
Female	18 52.9%
Male	16 47.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Progression Free Survival (PFS)
Description	The primary efficacy endpoint is progression-free survival at 12 weeks after start of therapy. A progression-free survival rate at 12 weeks will be calculated, with patients categorized in a dichotomous manner as alive and progression-free or in progression or dead at 12 weeks.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	34
Progression-Free & Alive	32.4 95.3%
Progressed, Died, or Unknown	67.6 198.8%

2. Secondary Outcome

Title	Duration of Overall Survival
Description	The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time Frame	From start of treatment to death; up to the time that all participants ended treatment

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	0

3. Secondary Outcome

Title	Participants Achieving Objective Response
Description	Objective response is defined as a complete response (CR) or partial response (PR) that has been confirmed by a second tumor assessment no earlier than 4 weeks after the initial documentation. Response is assessed using Response Evaluation Criteria in Solid Tumors (RECIST)criteria. The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time Frame	Patients were followed from start of therapy until date of first response

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	0

4. Secondary Outcome

Title	Time to Best Response
Description	This is defined as time from the start of therapy to the date of first CR or PR. The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time Frame	Patients were followed from start of therapy until date of first response

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	0

5. Secondary Outcome

Title	Time to Progressive Disease (PD)
Description	The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time Frame	From start of therapy to the date of first documentation of PD. Pts who never progress prior to final analysis or are withdrawn from the study without documented progression will be censored at the date of the last valid tumor assessment.

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	0

6. Secondary Outcome

Title	Duration of Objective Response
Description	This is defined similarly for complete and partial responders. Complete response or partial response lasts from the date the complete response or partial response was first recorded to the date on which progressive disease is first noted or date of death. If a patient does not progress or die while being followed, the date of the last valid tumor assessment will be taken. The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time Frame	from the date the complete or partial response was first recorded to the date which progressive disease is first noted or date of death. If a patient does not progress or die while being followed, the date of the last valid tumor assessment will be taken

Outcome Measure Data

Analysis Population Description

All Treated Population

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	0

7. Secondary Outcome

Title	Baseline Electrocardiogram (ECG)
Description	Standard safety monitoring includes baseline Electrocardiogram (ECG). The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed. The study was prematurely terminated due to discontinuation of R1507 development (not for safety reasons). As a result, data not provided for outcome measures listed.
Time Frame	baseline within 28 days of starting treatment (screening visit).

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	0

8. Secondary Outcome

Title	Fasting Glucose, Highest Post-Baseline Value
Description	A fasting glucose was required at baseline, and random non-fasting glucose testing was performed weekly for the first 6 weeks followed by day 1 of each 3 week treatment phase. The number of participants with the highest post-baseline fasting glucose level at any time point post baseline relative to the participant's baseline glucose level is reported.
Time Frame	Baseline, Highest Post-Baseline value within the timeframe of post-baseline collection up to when patient discontinued (up to 59 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population: based on the total number of participants n = 34

Arm/Group Title	R1507_Baseline Glucose Normal	R1507_Baseline Impaired Fasting Glucose	R1507_Baseline Diabetes Mellitus	R1507_Baseline Missing
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO) Includes all participants with a fasting glucose at baseline < 110 mg/dL.	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO) Includes all participants with a fasting glucose at baseline ≥ 110 to < 126 mg/dL	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO) Includes all participants with a fasting glucose at baseline ≥ 126 mg/dL	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO) Includes all participants with missing fasting glucose at baseline
Measure Participants	26	4	2	2
Normal (< 140 mg/dL)	21 61.8%	3 NaN	1 NaN	0 NaN
Impaired Fasting Glucose (≥ 140 to ≤ 200 mg/dL)	2 5.9%	1 NaN	1 NaN	0 NaN
Diabetes Mellitus (> 200 mg/dL)	0 0%	0 NaN	0 NaN	0 NaN
Missing	3 8.8%	0 NaN	0 NaN	2 NaN

9. Secondary Outcome

Title	Hemoglobin A1c (HbA1c)
Description	Standard safety monitoring includes baseline Electrocardiogram (ECG), Fasting glucose and HbA1c, monthly urine pregnancy test in female patients of childbearing potential and Human anti-human antibody (HAHA) testing. Data will be represented in the Serious Adverse Event (SAE) Adverse Event (AE) section of Protocol Registration System (PRS).
Time Frame	screening

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	0

10. Secondary Outcome

Title	Monthly Urine Pregnancy Test in Female Patients of Childbearing Potential
Description	Standard safety monitoring includes baseline Electrocardiogram (ECG), Fasting glucose and HbA1c, monthly urine pregnancy test in female patients of childbearing potential and Human anti-human antibody (HAHA) testing. Not posted; it will be represented in the Serious Adverse Event (SAE) Adverse Event (AE) section of Protocol Registration System (PRS).
Time Frame	Within 7 days of starting treatment (baseline visit)

Outcome Measure Data

Analysis Population Description

Female patients of childbearing potential

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	0

11. Secondary Outcome

Title	Number of Participants With Positive Results for Human Anti-human Antibody (HAHA) Testing
Description	Number of participants who tested positive for Human anti-human antibody (HAHA) testing for immunogenicity. To determine HAHA specificity, screened positive samples were tested in a confirmatory assay in the presence of 10 ug/mL R1507. Samples with > 19.7% inhibition were considered true positives, whereas those with < 19.7% inhibition were considered to be false positives.
Time Frame	prior to dosing on week 1 (day 1), week 4 (day 22), week 10 (day 64), final visit, follow up visit and 12 weeks post last dose (up to 71 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	6
POSITIVE	1 2.9%
FALSE POSITIVE	5 14.7%

12. Secondary Outcome

Title	Electrocardiogram (ECG)
Description	12 lead ECG is required at baseline and will be measured during the trial as clinically indicated at the discretion of the investigators. For each reading, QTcF value will be calculated as the QT value (seconds) divided by the cube root of the RR interval in seconds (Fridericia correction). A listing will be generated showing, for each patient, the visits at which ECGs were taken and the results (normal or abnormal, as well as any comments provided).
Time Frame	baseline and thereafter as clinically indicated at the discretion of the investigator up to the time that the patient discontinued (up to 59 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	34
Summary of QTcF Interval (n = 2)	421.5 (3.54)
Change from Baseline (n = 1)	24.0 (NA)

13. Secondary Outcome

Title	Population Pharmacokinetics of R1507 and Tarceva
Description	Population PK of R1507 and erlotinib were planned but not analyzed due to the termination of the trial.
Time Frame	Throughout study

Outcome Measure Data

Analysis Population Description

Population PK of R1507 and erlotinib

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	0

14. Secondary Outcome

Title	Assessment of Potential Predictive and Prognostic Biomarkers.
Description	Total IGF-I, free IGF I/II and other potential biomarkers present in serum. Further putative biomarker analyses in blood and tumor samples were planned in the protocol for exploratory assessment of correlation with clinical outcome. None of these were analyzed due to the termination of the trial.
Time Frame	Throughout study

Outcome Measure Data

Analysis Population Description

Responders and non-responders

Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
Measure Participants	0

Adverse Events

Time Frame	From start of treatment until 30 days after last dose (up to 64 weeks) or if the AE was related to study drug, up until the AE resolved
Arm/Group Title	R1507
Arm/Group Description	9 mg/kg once a week (qw) IV administered over 60-90 minutes erlotinib - 150 mg Once daily administration (qd) Oral administration(PO)
All Cause Mortality
	R1507
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	R1507
	Affected / at Risk (%)	# Events
Total	12/34 (35.3%)
Blood and lymphatic system disorders
THROMBOTIC MICROANGIOPATHY	1/34 (2.9%)
Cardiac disorders
MYOCARDIAL INFARCTION	1/34 (2.9%)
General disorders
ASTHENIA	1/34 (2.9%)
GENERAL PHYSICAL HEALTH DETERIORATION	1/34 (2.9%)
MUCOSAL INFLAMMATION	1/34 (2.9%)
PAIN	1/34 (2.9%)
Infections and infestations
PNEUMONIA	1/34 (2.9%)
Metabolism and nutrition disorders
HYPERGLYCAEMIA	1/34 (2.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER	1/34 (2.9%)
Nervous system disorders
CONVULSION	1/34 (2.9%)
DISTURBANCE IN ATTENTION	1/34 (2.9%)
EPILEPSY	1/34 (2.9%)
Psychiatric disorders
CONFUSIONAL STATE	1/34 (2.9%)
Reproductive system and breast disorders
PROSTATITIS	1/34 (2.9%)
Respiratory, thoracic and mediastinal disorders
LUNG DISORDER	1/34 (2.9%)
PULMONARY EMBOLISM	1/34 (2.9%)
Vascular disorders
DEEP VEIN THROMBOSIS	1/34 (2.9%)
Other (Not Including Serious) Adverse Events
	R1507
	Affected / at Risk (%)	# Events
Total	33/34 (97.1%)
Blood and lymphatic system disorders
EPISTAXIS	3/34 (8.8%)
ANAEMIA	2/34 (5.9%)
HAEMOPTYSIS	2/34 (5.9%)
Ear and labyrinth disorders
VERTIGO	2/34 (5.9%)
Eye disorders
CONJUNCTIVITIS	3/34 (8.8%)
Gastrointestinal disorders
DIARRHOEA	15/34 (44.1%)
VOMITING	7/34 (20.6%)
NAUSEA	6/34 (17.6%)
CONSTIPATION	4/34 (11.8%)
ABDOMINAL PAIN	3/34 (8.8%)
ABDOMINAL PAIN UPPER	3/34 (8.8%)
MUCOSAL INFLAMMATION	2/34 (5.9%)
General disorders
ASTHENIA	18/34 (52.9%)
DECREASED APPETITE	15/34 (44.1%)
NECK PAIN	3/34 (8.8%)
PARONYCHIA	3/34 (8.8%)
CHEST PAIN	2/34 (5.9%)
DYSGEUSIA	2/34 (5.9%)
DYSPHONIA	2/34 (5.9%)
HEADACHE	2/34 (5.9%)
PYREXIA	2/34 (5.9%)
WEIGHT DECREASED	2/34 (5.9%)
Metabolism and nutrition disorders
BLOOD MAGNESIUM DECREASED	2/34 (5.9%)
Musculoskeletal and connective tissue disorders
MUSCLE SPASMS	9/34 (26.5%)
BONE PAIN	3/34 (8.8%)
MUSCULOSKELETAL CHEST PAIN	2/34 (5.9%)
MUSCULOSKELETAL PAIN	2/34 (5.9%)
Nervous system disorders
MYALGIA	3/34 (8.8%)
FATIGUE	2/34 (5.9%)
Psychiatric disorders
DEPRESSION	3/34 (8.8%)
SOMNOLENCE	2/34 (5.9%)
Renal and urinary disorders
URINARY TRACT INFECTION	3/34 (8.8%)
RENAL FAILURE	2/34 (5.9%)
Respiratory, thoracic and mediastinal disorders
COUGH	9/34 (26.5%)
BRONCHITIS	3/34 (8.8%)
DYSPNOEA	2/34 (5.9%)
DYSPNOEA EXERTIONAL	2/34 (5.9%)
NASAL DRYNESS	2/34 (5.9%)
PRESYNCOPE	2/34 (5.9%)
Skin and subcutaneous tissue disorders
RASH	6/34 (17.6%)
NAIL TOXICITY	5/34 (14.7%)
SKIN TOXICITY	5/34 (14.7%)
DRY SKIN	4/34 (11.8%)
ACNE	2/34 (5.9%)
NAIL DISORDER	2/34 (5.9%)
SKIN REACTION	2/34 (5.9%)
Vascular disorders
HYPERTENSION	2/34 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.