Study of Dalantercept in Patients With Squamous Cell Carcinoma of the Head and Neck

• Sponsor: Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.) (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01458392
• Collaborator: (none)
• Enrollment: 46
• Locations: 8
• Arm: 1
• Duration (Months): 47
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Dalantercept, a soluble form of the activin receptor-like kinase-1 protein, is being studied in patients with squamous cell carcinoma of the head and neck (SCCHN). Dalantercept blocks the development of blood vessels that supply tumors.

Condition or Disease	Intervention/Treatment	Phase
Squamous Cell Carcinoma of the Head and Neck	Biological: Dalantercept	Phase 2

Detailed Description

For cancer cells to grow, they need to have nutrients supplied to them through blood vessels. The study drug, dalantercept, is designed to work by blocking the growth of those blood vessels and preventing cancer cells from growing. The purpose of this study is to find out if dalantercept can cause SCCHN tumors to shrink or stop growing. This study will also evaluate the safety of dalantercept in patients with SCCHN.

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label Phase 2 Study of Dalantercept in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dalantercept dalantercept	Biological: Dalantercept; Subcutaneous dose of dalantercept once every 3 weeks.

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [Tumor assessments performed every 6 weeks, up to 30 days after the last dose of dalantercept and/or disease progression, up to approximately 2 years.]

   ORR is defined as the proportion of patients who met criteria for complete response or partial response. Patients were evaluable for ORR if they had at least one measurable lesion at baseline and at least one disease assessment after baseline. RECIST version 1.1 was used to evaluate efficacy. In addition, patients who developed clinical or radiological progression of disease prior to the scheduled tumor assessment were also considered evaluable for response. The response rate was estimated as the proportion of patients evaluable for response who meet the criteria for complete (CR) and partial response (PR). Per RECIST v1.1 for target lesions and assessed by MRI: complete response (CR), disappearance of all target lesions; partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR + PR.

Secondary Outcome Measures

1. Safety and Tolerability [Adverse events captured from first dose of dalantercept through 30 days after last dose of dalantercept.]

   Number of participants with at least one adverse event as a measure of safety and tolerability.

2. Dalantercept Serum Concentration After Single and Multiple Doses [Up to 43 days from initiation of treatment.]

   Pharmacokinetic samples were collected pre- and post- dose on Days: 1, 8, 15, 22, 29, and 43. Reported below is AUC0-t (cycle 1).

3. Dalantercept Serum Concentration After Single and Multiple Doses [Up to 43 days from initiation of treatment.]

   Pharmacokinetic samples were collected pre- and post- dose on Days: 1, 8, 15, 22, 29, and 43. Reported below is Cmax (cycle 1).

4. Progression Free Survival (PFS) [Tumor assessments performed every 6 weeks, up to 30 days after the last dose of dalantercept and/or disease progression, up to approximately 2 years.]

   PFS is defined as the date of the first dose to the first observation of disease progression (according to RECIST v.1.1) or death due to any cause. Progression is defined using RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

5. Overall Survival (OS) [Survival captured until death or at a minimum 1 year from first dose of dalantercept.]

   OS is calculated as the number of months from date of the first dose to the date of death. The last patient treated will be followed for overall survival for 1 year following treatment initiation.

6. Disease Control Rate [Tumor assessments performed every 6 weeks, up to 30 days after the last dose of dalantercept and/or disease progression, up to approximately 2 years.]

   Disease control rate will be estimated as the proportion of patients evaluable for response who meet the criteria for complete response, partial response, or stable disease.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Histologically and/or cytologically confirmed, recurrent or metastatic SCCHN of mucosal origin (oral cavity, oropharynx, hypopharynx or larynx) not amenable to further local therapy (surgery, or radiation including re-irradiation); patients with unknown primary SCCHN presumed to be of head and neck mucosal origin are eligible if they meet all other entry criteria.

• Previously treated with at least one platinum-containing regimen or contraindicated for treatment with a platinum containing therapy. (Note: platinum therapy can occur upfront or after recurrence of disease. Failure of platinum therapy is not required.)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Key Exclusion Criteria:

• Nasopharyngeal carcinoma, paranasal sinus, salivary gland or primary skin SCCHN.

• Any other active malignancy for which chemotherapy or other anti-cancer therapy is indicated.

• Chemotherapy or other anti-cancer therapy or radiation therapy within 5 times the half-life of the drug or within 3 weeks prior to study day 1 if the half-life is not known.

• Treatment with another investigational drug or device, or approved therapy for investigational use, within 5 times the half-life of the drug or within 3 weeks prior to study day 1 if the half-life is not known.

• Major surgery within 4 weeks prior to study day 1 (patients must have recovered completely from any previous surgery prior to study day 1).

• Clinically significant cardiovascular risk.

• Clinically significant active pulmonary risk.

• Clinically significant active bleeding.

• Peripheral edema ≥ Grade 1 within 4 weeks prior to study day 1.

• Pregnant or lactating female patients.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Acceleron Investigative Site	Aurora	Colorado	United States
2	Acceleron Investigative Site	Atlanta	Georgia	United States
3	Acceleron Investigative Site	Boston	Massachusetts	United States
4	Acceleron Investigative Site	Detroit	Michigan	United States
5	Acceleron Investigative Site	New York	New York	United States
6	Acceleron Investigative Site	Philadelphia	Pennsylvania	United States
7	Acceleron Investigative Site	San Antonio	Texas	United States
8	Acceleron Investigative Site	Salt Lake City	Utah	United States

Sponsors and Collaborators

• Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Acceleron Pharma Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)
• ClinicalTrials.gov Identifier: NCT01458392
• Other Study ID Numbers: A041-03; dalantercept
• First Posted: Oct 24, 2011
• Last Update Posted: Jun 27, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck

Study Results

Participant Flow

Arm/Group Title	Dalantercept 80 mg	Dalantercept 0.6 mg/kg	Dalantercept 1.2 mg/kg
Arm/Group Description	Subcutaneous 80 mg dose of dalantercept once every 3 weeks.	Subcutaneous 0.6 mg/kg dose of dalantercept once every 3 weeks.	Subcutaneous 1.2 mg/kg dose of dalantercept once every 3 weeks.
Period Title: Overall Study
STARTED	2	13	31
COMPLETED	0	0	0
NOT COMPLETED	2	13	31

Baseline Characteristics

Arm/Group Title	Dalantercept 80 mg	Dalantercept 0.6 mg/kg	Dalantercept 1.2 mg/kg	Total
Arm/Group Description	Subcutaneous 80 mg dose of dalantercept once every 3 weeks.	Subcutaneous 0.6 mg/kg dose of dalantercept once every 3 weeks.	Subcutaneous 1.2 mg/kg dose of dalantercept once every 3 weeks.	Total of all reporting groups
Overall Participants	2	13	31	46
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.5 (13.4)	59.6 (5.1)	61.1 (9.5)	60.5 (8.5)
Sex: Female, Male (Count of Participants)
Female	2 100%	0 0%	5 16.1%	7 15.2%
Male	0 0%	13 100%	26 83.9%	39 84.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 15.4%	0 0%	2 4.3%
Not Hispanic or Latino	2 100%	11 84.6%	31 100%	44 95.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	3 9.7%	3 6.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	7 22.6%	7 15.2%
White	2 100%	13 100%	19 61.3%	34 73.9%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	2 6.5%	2 4.3%
Region of Enrollment (participants) [Number]
United States	2 100%	13 100%	31 100%	46 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	ORR is defined as the proportion of patients who met criteria for complete response or partial response. Patients were evaluable for ORR if they had at least one measurable lesion at baseline and at least one disease assessment after baseline. RECIST version 1.1 was used to evaluate efficacy. In addition, patients who developed clinical or radiological progression of disease prior to the scheduled tumor assessment were also considered evaluable for response. The response rate was estimated as the proportion of patients evaluable for response who meet the criteria for complete (CR) and partial response (PR). Per RECIST v1.1 for target lesions and assessed by MRI: complete response (CR), disappearance of all target lesions; partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR + PR.
Time Frame	Tumor assessments performed every 6 weeks, up to 30 days after the last dose of dalantercept and/or disease progression, up to approximately 2 years.

Outcome Measure Data

Analysis Population Description

The two patients at the 80 mg, fixed-dose level were excluded from the efficacy analysis as the protocol had been amended to incorporate weight-based dosing for the remainder of the study population. 40 received at least one dose of study drug in either the 0.6 mg/kg or 1.2 mg/kg dose groups and had at least one on-treatment tumor assessment.

Arm/Group Title	Dalantercept 0.6 mg/kg	Dalantercept 1.2 mg/kg
Arm/Group Description	Subcutaneous 0.6-mg/kg dose of dalantercept once every 3 weeks.	Subcutaneous 1.2-mg/kg dose of dalantercept once every 3 weeks.
Measure Participants	13	27
Number (95% Confidence Interval) [participants]	0 0%	2 15.4%

2. Secondary Outcome

Title	Safety and Tolerability
Description	Number of participants with at least one adverse event as a measure of safety and tolerability.
Time Frame	Adverse events captured from first dose of dalantercept through 30 days after last dose of dalantercept.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dalantercept 80 mg	Dalantercept 0.6 mg/kg	Dalantercept 1.2 mg/kg
Arm/Group Description	Subcutaneous 80 mg dose of dalantercept once every 3 weeks.	Subcutaneous 0.6 mg/kg dose of dalantercept once every 3 weeks.	Subcutaneous 1.2 mg/kg dose of dalantercept once every 3 weeks.
Measure Participants	2	13	31
Number [participants]	2 100%	13 100%	31 100%

3. Secondary Outcome

Title	Dalantercept Serum Concentration After Single and Multiple Doses
Description	Pharmacokinetic samples were collected pre- and post- dose on Days: 1, 8, 15, 22, 29, and 43. Reported below is AUC0-t (cycle 1).
Time Frame	Up to 43 days from initiation of treatment.

Outcome Measure Data

Analysis Population Description

The two patients at the 80 mg, fixed-dose level were excluded from the efficacy analysis as the protocol was amended to incorporate weight-based dosing for the remainder of the study population. 2 patients in the 0.6-mg/kg and 6 in the 1.2-mg/kg cohort had less than 2 measurable serum dalantercept concentrations and were excluded from PK analysis.

Arm/Group Title	Dalantercept 0.6 mg/kg	Dalantercept 1.2 mg/kg
Arm/Group Description	Subcutaneous 0.6 mg/kg dose of dalantercept once every 3 weeks.	Subcutaneous 1.2 mg/kg dose of dalantercept once every 3 weeks.
Measure Participants	12	26
Geometric Mean (Geometric Coefficient of Variation) [ng*day/mL]	32992 (35.1)	69572 (44.7)

4. Secondary Outcome

Title	Dalantercept Serum Concentration After Single and Multiple Doses
Description	Pharmacokinetic samples were collected pre- and post- dose on Days: 1, 8, 15, 22, 29, and 43. Reported below is Cmax (cycle 1).
Time Frame	Up to 43 days from initiation of treatment.

Outcome Measure Data

Analysis Population Description

The two patients at the 80 mg, fixed-dose level were excluded from the efficacy analysis as the protocol was amended to incorporate weight-based dosing for the remainder of the study population. 2 patients in the 0.6-mg/kg and 6 in the 1.2-mg/kg cohort had less than 2 measurable serum dalantercept concentrations and were excluded from PK analysis.

Arm/Group Title	Dalantercept 0.6 mg/kg	Dalantercept 1.2 mg/kg
Arm/Group Description	Subcutaneous 0.6 mg/kg dose of dalantercept once every 3 weeks.	Subcutaneous 1.2 mg/kg dose of dalantercept once every 3 weeks.
Measure Participants	12	26
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	2446 (35.1)	5336 (37.8)

5. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS is defined as the date of the first dose to the first observation of disease progression (according to RECIST v.1.1) or death due to any cause. Progression is defined using RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	Tumor assessments performed every 6 weeks, up to 30 days after the last dose of dalantercept and/or disease progression, up to approximately 2 years.

Outcome Measure Data

Analysis Population Description

The two patients at the 80 mg, fixed-dose level were excluded from the efficacy analysis as the protocol had been amended to incorporate weight-based dosing for the remainder of the study population.

Arm/Group Title	Dalantercept 0.6 mg/kg	Dalantercept 1.2 mg/kg
Arm/Group Description	Subcutaneous 0.6 mg/kg dose of dalantercept once every 3 weeks.	Subcutaneous 1.2 mg/kg dose of dalantercept once every 3 weeks.
Measure Participants	13	31
Median (95% Confidence Interval) [weeks]	5.8	6.1

6. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is calculated as the number of months from date of the first dose to the date of death. The last patient treated will be followed for overall survival for 1 year following treatment initiation.
Time Frame	Survival captured until death or at a minimum 1 year from first dose of dalantercept.

Outcome Measure Data

Analysis Population Description

The two patients at the 80 mg, fixed-dose level were excluded from the efficacy analysis as the protocol had been amended to incorporate weight-based dosing for the remainder of the study population.

Arm/Group Title	Dalantercept 0.6 mg/kg	Dalantercept 1.2 mg/kg
Arm/Group Description	Subcutaneous 0.6 mg/kg dose of dalantercept once every 3 weeks.	Subcutaneous 1.2 mg/kg dose of dalantercept once every 3 weeks.
Measure Participants	13	31
Median (95% Confidence Interval) [weeks]	30.9	41.3

7. Secondary Outcome

Title	Disease Control Rate
Description	Disease control rate will be estimated as the proportion of patients evaluable for response who meet the criteria for complete response, partial response, or stable disease.
Time Frame	Tumor assessments performed every 6 weeks, up to 30 days after the last dose of dalantercept and/or disease progression, up to approximately 2 years.

Outcome Measure Data

Analysis Population Description

The two patients at the 80 mg, fixed-dose level were excluded from the efficacy analysis as the protocol had been amended to incorporate weight-based dosing for the remainder of the study population. 40 received at least one dose of study drug in either the 0.6 mg/kg or 1.2 mg/kg dose groups and had at least one on-treatment tumor assessment.

Arm/Group Title	Dalantercept 0.6 mg/kg	Dalantercept 1.2 mg/kg
Arm/Group Description	Subcutaneous 0.6 mg/kg dose of dalantercept once every 3 weeks.	Subcutaneous 1.2 mg/kg dose of dalantercept once every 3 weeks.
Measure Participants	13	27
Number (95% Confidence Interval) [percentage of participants]	30.8 1540%	44.4 341.5%

Adverse Events

Arm/Group Title	Dalantercept 80 mg		Dalantercept 0.6 mg/kg		Dalantercept 1.2 mg/kg
Arm/Group Description	Subcutaneous 80 mg dose of dalantercept once every 3 weeks.		Subcutaneous 0.6 mg/kg dose of dalantercept once every 3 weeks.		Subcutaneous 1.2 mg/kg dose of dalantercept once every 3 weeks.
All Cause Mortality
	Dalantercept 80 mg		Dalantercept 0.6 mg/kg		Dalantercept 1.2 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Dalantercept 80 mg		Dalantercept 0.6 mg/kg		Dalantercept 1.2 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/2 (50%)		6/13 (46.2%)		6/31 (19.4%)
General disorders
Disease progression	0/2 (0%)		1/13 (7.7%)		2/31 (6.5%)
Infections and infestations
Pneumonia	0/2 (0%)		0/13 (0%)		1/31 (3.2%)
Injury, poisoning and procedural complications
Tracheal obstruction	0/2 (0%)		0/13 (0%)		1/31 (3.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tongue cancer metastatic	1/2 (50%)		0/13 (0%)		0/31 (0%)
Metastases to central nervous system	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Tumour compression	0/2 (0%)		0/13 (0%)		1/31 (3.2%)
Nervous system disorders
Spinal cord compression	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Psychiatric disorders
Suicide attempt	0/2 (0%)		0/13 (0%)		1/31 (3.2%)
Renal and urinary disorders
Renal failure acute	0/2 (0%)		0/13 (0%)		1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/2 (0%)		1/13 (7.7%)		1/31 (3.2%)
Aspiration	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Pneumonia aspiration	0/2 (0%)		0/13 (0%)		1/31 (3.2%)
Pulmonary oedema	0/2 (0%)		0/13 (0%)		1/31 (3.2%)
Respiratory distress	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Dalantercept 80 mg		Dalantercept 0.6 mg/kg		Dalantercept 1.2 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		13/13 (100%)		31/31 (100%)
Blood and lymphatic system disorders
Anaemia	0/2 (0%)		2/13 (15.4%)		16/31 (51.6%)
Leukopenia	0/2 (0%)		0/13 (0%)		3/31 (9.7%)
Thrombocytopenia	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Leukocytosis	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Lymphadenopathy	1/2 (50%)		0/13 (0%)		0/31 (0%)
Cardiac disorders
Pericardial effusion	0/2 (0%)		1/13 (7.7%)		1/31 (3.2%)
Left ventricular dysfunction	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Eye disorders
Lacrimation increased	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Macular degeneration	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Gastrointestinal disorders
Constipation	1/2 (50%)		3/13 (23.1%)		2/31 (6.5%)
Nausea	1/2 (50%)		1/13 (7.7%)		4/31 (12.9%)
Vomiting	1/2 (50%)		2/13 (15.4%)		3/31 (9.7%)
Abdominal pain	0/2 (0%)		1/13 (7.7%)		3/31 (9.7%)
Dysphagia	0/2 (0%)		2/13 (15.4%)		2/31 (6.5%)
Dry mouth	0/2 (0%)		1/13 (7.7%)		2/31 (6.5%)
Diarrhoea	1/2 (50%)		1/13 (7.7%)		0/31 (0%)
Tongue oedema	0/2 (0%)		1/13 (7.7%)		1/31 (3.2%)
Flatulence	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Gingivitis	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Glossodynia	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Paraesthesia oral	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Salivary hypersecretion	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
General disorders
Fatigue	1/2 (50%)		8/13 (61.5%)		12/31 (38.7%)
Oedema peripheral	0/2 (0%)		2/13 (15.4%)		11/31 (35.5%)
Face oedema	0/2 (0%)		0/13 (0%)		5/31 (16.1%)
Oedema	1/2 (50%)		2/13 (15.4%)		1/31 (3.2%)
Pyrexia	0/2 (0%)		0/13 (0%)		4/31 (12.9%)
Malaise	0/2 (0%)		1/13 (7.7%)		1/31 (3.2%)
Non-cardiac chest pain	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Pain	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Catheter site pain	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Injection site pain	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Infections and infestations
Pneumonia	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Sinusitis	1/2 (50%)		0/13 (0%)		1/31 (3.2%)
Candidiasis	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Oral candidiasis	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Staphylococcal infection	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Wound infection	1/2 (50%)		0/13 (0%)		0/31 (0%)
Injury, poisoning and procedural complications
Abdominal wound dehiscence	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Feeding tube complication	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Laceration	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Wound haemorrhage	1/2 (50%)		0/13 (0%)		0/31 (0%)
Investigations
Blood alkaline phosphatase increased	0/2 (0%)		1/13 (7.7%)		3/31 (9.7%)
Weight increased	0/2 (0%)		0/13 (0%)		4/31 (12.9%)
Weight decreased	0/2 (0%)		3/13 (23.1%)		0/31 (0%)
Aspartate aminotransferase increased	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Brain natriuretic peptide increased	0/2 (0%)		1/13 (7.7%)		1/31 (3.2%)
Lipase increase	0/2 (0%)		1/13 (7.7%)		1/31 (3.2%)
Blood urea increased	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Protein total decreased	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Troponin increased	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
N-terminal prohormone brain natriuretic peptide increased	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Metabolism and nutrition disorders
Hyponatraemia	1/2 (50%)		1/13 (7.7%)		9/31 (29%)
Decreased appetite	0/2 (0%)		3/13 (23.1%)		5/31 (16.1%)
Hyperglycaemia	0/2 (0%)		0/13 (0%)		6/31 (19.4%)
Hypoalbuminaemia	0/2 (0%)		2/13 (15.4%)		3/31 (9.7%)
Hyperkalaemia	0/2 (0%)		1/13 (7.7%)		2/31 (6.5%)
Hypokalaemia	1/2 (50%)		0/13 (0%)		2/31 (6.5%)
Dehydration	1/2 (50%)		1/13 (7.7%)		0/31 (0%)
Hypercalcaemia	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/2 (0%)		0/13 (0%)		6/31 (19.4%)
Back pain	0/2 (0%)		0/13 (0%)		3/31 (9.7%)
Myalgia	0/2 (0%)		1/13 (7.7%)		2/31 (6.5%)
Neck pain	0/2 (0%)		0/13 (0%)		3/31 (9.7%)
Flank pain	0/2 (0%)		1/13 (7.7%)		1/31 (3.2%)
Joint swelling	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Musculoskeletal chest pain	0/2 (0%)		1/13 (7.7%)		1/31 (3.2%)
Pain in jaw	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Pain in extremity	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/2 (0%)		1/13 (7.7%)		1/31 (3.2%)
Nervous system disorders
Headache	1/2 (50%)		4/13 (30.8%)		11/31 (35.5%)
Neuropathy peripheral	0/2 (0%)		0/13 (0%)		4/31 (12.9%)
Paresthesia	0/2 (0%)		1/13 (7.7%)		3/31 (9.7%)
Dizziness	0/2 (0%)		1/13 (7.7%)		1/31 (3.2%)
Somnolence	0/2 (0%)		2/13 (15.4%)		0/31 (0%)
Balance disorder	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Dysarthria	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Radiculopathy	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Psychiatric disorders
Insomnia	0/2 (0%)		1/13 (7.7%)		3/31 (9.7%)
Anxiety	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Depression	0/2 (0%)		1/13 (7.7%)		1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/2 (0%)		2/13 (15.4%)		5/31 (16.1%)
Cough	0/2 (0%)		2/13 (15.4%)		4/31 (12.9%)
Pleural effusion	0/2 (0%)		1/13 (7.7%)		4/31 (12.9%)
Oropharyngeal pain	0/2 (0%)		0/13 (0%)		3/31 (9.7%)
Dysphonia	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Dysphonia exertional	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Epistaxis	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Nasal congestion	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Wheezing	0/2 (0%)		2/13 (15.4%)		0/31 (0%)
Pneumothorax	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Pulmonary hypertension	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Rhonchi	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Sputum increased	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Skin and subcutaneous tissue disorders
Telangiectasia	0/2 (0%)		1/13 (7.7%)		3/31 (9.7%)
Pruritus	0/2 (0%)		2/13 (15.4%)		1/31 (3.2%)
Rash	0/2 (0%)		0/13 (0%)		2/31 (6.5%)
Dermatitis acneiform	0/2 (0%)		1/13 (7.7%)		0/31 (0%)
Vascular disorders
Hypotension	0/2 (0%)		1/13 (7.7%)		3/31 (9.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.