Oral Topotecan to Treat Recurrent or Persistent Solid Tumors

• Sponsor: Accelerated Community Oncology Research Network (Other)
• Overall Status: Completed
• CT.gov ID: NCT00382733
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 26
• Location: 1
• Duration (Months): 51.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effectiveness of oral topotecan and how well the chemotherapy is tolerated (any side effects) when it is given in different dose levels. The study will also collect information on how the medication is being broken down and absorbed in the body and how quality of life is affected during treatment.

Condition or Disease	Intervention/Treatment	Phase
Tumors	Drug: Oral Topotecan	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Oral Topotecan, Utilization for a Metronomic Dosing Schedule to Treat Recurrent or Persistent Solid Tumors
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of Single Agent Metronomic Oral Topotecan [MTD was assessed during the first cycle of treatment (days 1-28).]

   The MTD of metronomic oral topotecan was determined using a standard 3+3 dose escalation cohort design. The total sample and the number of subjects who receive each dose in this design depends on the frequency of dose limiting toxicities (DLTs)at each dose level. If 0 out of 3 subjects experience a DLT at a given dose level, 3 subjects will be enrolled at the next higher dose level. If greater than or equal to 2 subjects experience a DLT at a given dose level, dose escalation will be stopped. If 1 out of 3 subjects experience a DLT at a given dose level, 3 subjects are enrolled at the same dose level.

Secondary Outcome Measures

1. Dose Limiting Toxicities (DLT) [DLTs were assessed during the first cycle of treatment (days 1-28).]

   DLTs were assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. This measure reports the number of subjects who experienced DLT at each dose level during the dose finding portion of the study.

2. Best Overall Response [Best overall response was assessed after every 8 weeks of treatment and at the end of treatment or time of disease progression, up to 1 year.]

   Best overall response is defined as the best response across all time points. Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of disease progression. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Patient provides written informed consent prior to study-specific screening procedures, with the understanding that the patient has the right to withdraw from the study at any time, without prejudice.

• Male or female patients.

• Patient is at least 18 years of age with recurrent or persistent solid tumors.

• Patient has adequate hematologic function (absolute neutrophil count [ANC] >= 1500/mL and platelets >= 100,000/mL), adequate renal function (serum creatinine < 2.0 mg/dL; calculated creatinine clearance > 40 mL/min), and adequate hepatic function (serum bilirubin <= 1.5 mg/dL and transaminases <= 3 times the upper limit of normal [3 x ULN]).

• Patient has Eastern Oncology Cooperative Group (ECOG) performance status of <= 2.

• Patient has a life expectancy of at least 3 months at time of enrollment.

• Patient has no medical problems, unrelated to the malignancy, of sufficient severity which would limit full compliance with the study or which would expose him/her to undue risks.

• Patient has received no more than 2 prior treatment regimens prior to enrollment including chemotherapy, hormonal therapy, biologic therapy, and immunotherapy.

• Patient has a negative serum or urine pregnancy test within 7 days prior to starting therapy (if a female of childbearing potential).

Exclusion Criteria:

• Patient is a pregnant or lactating woman. Women of childbearing potential with either a positive or no pregnant test (serum or urine) at baseline. Women of childbearing potential not using a reliable and appropriate contraceptive method will be excluded. (Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential.) Patients must agree to continue contraception for 30 days from the date of the last study drug administration.

• Patient has serious, uncontrolled, concurrent infection(s).

• Patient has received whole pelvic or extended field radiation therapy within 4 weeks of enrollment. Patients who have not fully recovered or whose acute toxicity related to prior radiotherapy has not returned to baseline are ineligible.

• Patient has received myelosuppressive chemotherapy within the last 4 weeks or has not recovered from the myelosuppressive effects of recent chemotherapy.

• Patient has received another investigational agent within 4 weeks prior to study enrollment.

• Patient has known hypersensitivity to topoisomerase I inhibitors.

• Patient is unable to swallow a capsule or has a disease known to affect drug absorption, such as short gut syndrome or active radiation enteritis.

• Patient has received drugs known to alter absorption such as antacids, proton pump blockers (eg, omeprazole), or H2 receptor antagonists (eg, cimetidine). A washout period of one week (7 days) is required prior to initiating study medication.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The West Clinic	Memphis	Tennessee	United States	38120

Sponsors and Collaborators

• Accelerated Community Oncology Research Network
• GlaxoSmithKline

Investigators

• Principal Investigator: Todd D. Tillmanns, M.D., West Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Accelerated Community Oncology Research Network
• ClinicalTrials.gov Identifier: NCT00382733
• Other Study ID Numbers: ACORN ATDTROC0501
• First Posted: Sep 29, 2006
• Last Update Posted: Jul 22, 2013
• Last Verified: Jul 1, 2013

• Keywords provided by Accelerated Community Oncology Research Network: Solid Tumors
• Additional relevant MeSH terms: Neoplasms; Topotecan

Study Results

Participant Flow

Recruitment Details	The study was open to enrollment at one community oncology clinic from November 2006 to May 2009.
Pre-assignment Detail	Informed consent was obtained from all subjects. All subjects underwent a screening period that could last up to 4 weeks during which pre-study assessments were completed. During the dose finding portion of the study, subjects were assigned to a Dose Level during enrollment. Once the MTD was determined, additional subjects were treated at the MTD.

Arm/Group Title	Oral Topotecan 0.25 mg Daily	Oral Topotecan 0.50 mg Daily	Oral Topotecan 0.75 mg Daily	Oral Topotecan 1.0 mg Daily	Oral Topotecan 1.25 mg Daily
Arm/Group Description	All subjects in this group were assigned to receive metronomic oral topotecan 0.25 mg daily (Dose Level 1).	All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2).	All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3).	All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4).	All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5).
Period Title: Overall Study
STARTED	3	4	3	14	2
COMPLETED	3	3	3	14	2
NOT COMPLETED	0	1	0	0	0

Baseline Characteristics

Arm/Group Title	Metronomic Oral Topotecan
Arm/Group Description	All subjects received metronomic oral topotecan daily at the assigned dose level.
Overall Participants	26
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.6 (8.99)
Sex: Female, Male (Count of Participants)
Female	20 76.9%
Male	6 23.1%
Region of Enrollment (participants) [Number]
United States	26 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Single Agent Metronomic Oral Topotecan
Description	The MTD of metronomic oral topotecan was determined using a standard 3+3 dose escalation cohort design. The total sample and the number of subjects who receive each dose in this design depends on the frequency of dose limiting toxicities (DLTs)at each dose level. If 0 out of 3 subjects experience a DLT at a given dose level, 3 subjects will be enrolled at the next higher dose level. If greater than or equal to 2 subjects experience a DLT at a given dose level, dose escalation will be stopped. If 1 out of 3 subjects experience a DLT at a given dose level, 3 subjects are enrolled at the same dose level.
Time Frame	MTD was assessed during the first cycle of treatment (days 1-28).

Outcome Measure Data

Analysis Population Description

DLT information was available for 3 subjects who received a topotecan dose of 0.25 mg/day, 3 subjects who received a topotecan dose of 0.50 mg/day, 3 subjects who received a topotecan dose of 0.75 mg/day, 3 subjects who received a topotecan dose of 1.0 mg/day, and 2 subjects who received a topotecan dose of 1.25 mg/day.

Arm/Group Title	Metronomic Oral Topotecan
Arm/Group Description	All subjects received metronomic oral topotecan daily at the assigned dose level.
Measure Participants	14
Number [mg/day]	1.0

2. Secondary Outcome

Title	Dose Limiting Toxicities (DLT)
Description	DLTs were assessed using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. This measure reports the number of subjects who experienced DLT at each dose level during the dose finding portion of the study.
Time Frame	DLTs were assessed during the first cycle of treatment (days 1-28).

Outcome Measure Data

Analysis Population Description

Number of participants analyzed refers to those for whom DLT information was available during the dose finding portion of the study.

Arm/Group Title	Oral Topotecan 0.25 mg Daily	Oral Topotecan 0.50 mg Daily	Oral Topotecan 0.75 mg Daily	Oral Topotecan 1.0 mg Daily	Oral Topotecan 1.25 mg Daily
Arm/Group Description	All subjects in this group were assigned to receive metronomic oral topotecan 0.25 mg daily (Dose Level 1).	All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2).	All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3).	All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4).	All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5).
Measure Participants	3	3	3	3	2
Number [participants]	0 0%	0 NaN	0 NaN	0 NaN	2 NaN

3. Secondary Outcome

Title	Best Overall Response
Description	Best overall response is defined as the best response across all time points. Response was evaluated via changes from baseline in radiological tumor measurements performed after every two treatment cycles and at the end of treatment or time of disease progression. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 guidelines, where complete response (CR) is the disappearance of all target lesions; partial response (PR) is >=30% decrease in the sum of the longest diameter (LD) of target lesions; Stable Disease (SD) is neither sufficient shrinkage in sum of LD of target lesions to be PR nor increase of >=20%; Progressive Disease (PD) is the increase in existing lesions or new lesions.
Time Frame	Best overall response was assessed after every 8 weeks of treatment and at the end of treatment or time of disease progression, up to 1 year.

Outcome Measure Data

Analysis Population Description

All enrolled subjects were analyzed for this outcome.

Arm/Group Title	Oral Topotecan 0.25 mg Daily	Oral Topotecan 0.50 mg Daily	Oral Topotecan 0.75 mg Daily	Oral Topotecan 1.0 mg Daily	Oral Topotecan 1.25 mg Daily
Arm/Group Description	All subjects in this group were assigned to receive metronomic oral topotecan 0.25 mg daily (Dose Level 1).	All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2).	All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3).	All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4).	All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5).
Measure Participants	3	4	3	14	2
Complete Response	0 0%	0 NaN	0 NaN	0 NaN	0 NaN
Partial Response	0 0%	0 NaN	0 NaN	1 NaN	0 NaN
Stable Disease	2 7.7%	1 NaN	2 NaN	4 NaN	0 NaN
Progressive Disease	0 0%	1 NaN	1 NaN	2 NaN	0 NaN
Not Evaluable	1 3.8%	2 NaN	0 NaN	7 NaN	2 NaN

Adverse Events

Time Frame	Adverse events were collected on day 1 of treatment until one month after the end of study treatment.
Adverse Event Reporting Description	Subjects were systematically assessed for adverse events on day 1 of each cycle by either the research coordinator, treating physician, or other appropriate sub-investigator.
Arm/Group Title	Oral Topotecan 0.25 mg Daily		Oral Topotecan 0.50 mg Daily		Oral Topotecan 0.75 mg Daily		Oral Topotecan 1.0 mg Daily		Oral Topotecan 1.25 mg Daily
Arm/Group Description	All subjects in this group were assigned to receive metronomic oral topotecan 0.25 mg daily (Dose Level 1).		All subjects in this group were assigned to receive metronomic oral topotecan 0.50 mg daily (Dose Level 2).		All subjects in this group were assigned to receive metronomic oral topotecan 0.75 mg daily (Dose Level 3).		All subjects in this group were assigned to receive metronomic oral topotecan 1.0 mg daily (Dose Level 4).		All subjects in this group were assigned to receive metronomic oral topotecan 1.25 mg daily (Dose Level 5).
All Cause Mortality
	Oral Topotecan 0.25 mg Daily		Oral Topotecan 0.50 mg Daily		Oral Topotecan 0.75 mg Daily		Oral Topotecan 1.0 mg Daily		Oral Topotecan 1.25 mg Daily
	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)
Serious Adverse Events
	Oral Topotecan 0.25 mg Daily		Oral Topotecan 0.50 mg Daily		Oral Topotecan 0.75 mg Daily		Oral Topotecan 1.0 mg Daily		Oral Topotecan 1.25 mg Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		7/14 (50%)		1/2 (50%)
Blood and lymphatic system disorders
Anemia	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Gastrointestinal disorders
Ascites	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		0/14 (0%)		0/2 (0%)
Intestinal obstruction	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Nausea	0/3 (0%)		0/4 (0%)		0/3 (0%)		0/14 (0%)		1/2 (50%)
Small intestinal obstruction	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
General disorders
Asthenia	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Infections and infestations
Infection	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Dehydration	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		1/2 (50%)
Hypokalemia	0/3 (0%)		0/4 (0%)		0/3 (0%)		0/14 (0%)		1/2 (50%)
Psychiatric disorders
Confusional state	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Delirium	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Reproductive system and breast disorders
Vaginal hemorrhage	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Oral Topotecan 0.25 mg Daily		Oral Topotecan 0.50 mg Daily		Oral Topotecan 0.75 mg Daily		Oral Topotecan 1.0 mg Daily		Oral Topotecan 1.25 mg Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		4/4 (100%)		3/3 (100%)		13/14 (92.9%)		2/2 (100%)
Blood and lymphatic system disorders
Anemia	2/3 (66.7%)		2/4 (50%)		1/3 (33.3%)		8/14 (57.1%)		0/2 (0%)
Neutropenia	0/3 (0%)		1/4 (25%)		0/3 (0%)		3/14 (21.4%)		0/2 (0%)
Thrombocytopenia	0/3 (0%)		0/4 (0%)		0/3 (0%)		2/14 (14.3%)		0/2 (0%)
Cardiac disorders
Tachycardia	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Ear and labyrinth disorders
Ear pain	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Eye disorders
Eye hemorrhage	0/3 (0%)		1/4 (25%)		0/3 (0%)		0/14 (0%)		0/2 (0%)
Vision blurred	0/3 (0%)		0/4 (0%)		0/3 (0%)		2/14 (14.3%)		0/2 (0%)
Gastrointestinal disorders
Abdominal distension	0/3 (0%)		1/4 (25%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Abdominal pain	0/3 (0%)		1/4 (25%)		0/3 (0%)		6/14 (42.9%)		0/2 (0%)
Abdominal pain lower	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		0/14 (0%)		0/2 (0%)
Abdominal pain upper	2/3 (66.7%)		0/4 (0%)		0/3 (0%)		2/14 (14.3%)		0/2 (0%)
Abdominal tenderness	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		0/14 (0%)		0/2 (0%)
Ascites	0/3 (0%)		1/4 (25%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Constipation	0/3 (0%)		2/4 (50%)		0/3 (0%)		6/14 (42.9%)		0/2 (0%)
Diarrhea	1/3 (33.3%)		1/4 (25%)		0/3 (0%)		3/14 (21.4%)		1/2 (50%)
Dry mouth	0/3 (0%)		1/4 (25%)		0/3 (0%)		0/14 (0%)		0/2 (0%)
Dyspepsia	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Dysphagia	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Nausea	2/3 (66.7%)		1/4 (25%)		0/3 (0%)		6/14 (42.9%)		1/2 (50%)
Small intestinal obstruction	1/3 (33.3%)		1/4 (25%)		0/3 (0%)		0/14 (0%)		0/2 (0%)
Vomiting	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		7/14 (50%)		1/2 (50%)
General disorders
Asthenia	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Chest pain	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		0/14 (0%)		0/2 (0%)
Fatigue	2/3 (66.7%)		3/4 (75%)		1/3 (33.3%)		7/14 (50%)		0/2 (0%)
Influenza like illness	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Peripheral edema	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Pain	0/3 (0%)		2/4 (50%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Pyrexia	0/3 (0%)		0/4 (0%)		0/3 (0%)		3/14 (21.4%)		0/2 (0%)
Hepatobiliary disorders
Jaundice	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Infections and infestations
Cellulitis	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Infection	0/3 (0%)		0/4 (0%)		0/3 (0%)		2/14 (14.3%)		0/2 (0%)
Oral candidiasis	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Urinary tract infection	1/3 (33.3%)		0/4 (0%)		1/3 (33.3%)		0/14 (0%)		0/2 (0%)
Investigations
Alanine aminotransferase increased	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Aspartate aminotransferase increased	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		1/14 (7.1%)		0/2 (0%)
Blood alkaline phosphatase increased	0/3 (0%)		1/4 (25%)		1/3 (33.3%)		1/14 (7.1%)		0/2 (0%)
Blood creatinine increased	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Neutrophil count decreased	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Neutrophil count increased	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Platelet count increased	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Waist circumference increased	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		0/14 (0%)		0/2 (0%)
Weight decreased	0/3 (0%)		0/4 (0%)		0/3 (0%)		3/14 (21.4%)		0/2 (0%)
Weight increased	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		0/14 (0%)		0/2 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/3 (0%)		0/4 (0%)		0/3 (0%)		4/14 (28.6%)		0/2 (0%)
Fluid overload	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Hypercalcemia	0/3 (0%)		2/4 (50%)		1/3 (33.3%)		0/14 (0%)		0/2 (0%)
Hyperkalemia	0/3 (0%)		1/4 (25%)		1/3 (33.3%)		0/14 (0%)		0/2 (0%)
Hypokalemia	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		1/14 (7.1%)		0/2 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/3 (0%)		0/4 (0%)		0/3 (0%)		2/14 (14.3%)		0/2 (0%)
Muscle spasms	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Musculoskeletal chest pain	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		0/14 (0%)		0/2 (0%)
Musculoskeletal pain	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		1/14 (7.1%)		0/2 (0%)
Pain in extremity	0/3 (0%)		1/4 (25%)		0/3 (0%)		0/14 (0%)		0/2 (0%)
Nervous system disorders
Cognitive disorder	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Dizziness	0/3 (0%)		0/4 (0%)		0/3 (0%)		2/14 (14.3%)		0/2 (0%)
Dysgeusia	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Headache	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		1/14 (7.1%)		0/2 (0%)
Lethargy	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Peripheral neuropathy	0/3 (0%)		0/4 (0%)		0/3 (0%)		2/14 (14.3%)		0/2 (0%)
Paresthesia	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Peripheral sensory neuropathy	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Restless leg syndrome	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		0/14 (0%)		0/2 (0%)
Sinus headache	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Psychiatric disorders
Depression	0/3 (0%)		1/4 (25%)		0/3 (0%)		0/14 (0%)		0/2 (0%)
Insomnia	1/3 (33.3%)		1/4 (25%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Nightmare	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		0/14 (0%)		0/2 (0%)
Renal and urinary disorders
Hydronephrosis	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Reproductive system and breast disorders
Perineal pain	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Vaginal hemorrhage	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Dyspnea	1/3 (33.3%)		0/4 (0%)		1/3 (33.3%)		0/14 (0%)		0/2 (0%)
Exertional dyspnea	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Oropharyngeal pain	1/3 (33.3%)		0/4 (0%)		0/3 (0%)		2/14 (14.3%)		0/2 (0%)
Rhinitis allergic	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Sinus congestion	0/3 (0%)		0/4 (0%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		0/14 (0%)		0/2 (0%)
Pruritus	0/3 (0%)		0/4 (0%)		1/3 (33.3%)		0/14 (0%)		0/2 (0%)
Rash	0/3 (0%)		1/4 (25%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Vascular disorders
Hypertension	0/3 (0%)		1/4 (25%)		0/3 (0%)		1/14 (7.1%)		0/2 (0%)
Hypotension	0/3 (0%)		0/4 (0%)		0/3 (0%)		3/14 (21.4%)		0/2 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.